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Abstract Several stomach diseases are attributed to the dysregulation of physiological function of gastric mucosal barrier by pathogens. Gastric organoids are a promising tool to develop treatment strategies for gastric infections. However, their functional features of in vivo gastric mucosal barrier and host–microbe interactions are limited due to the lack of physiological stimuli. Herein, a human stomach micro‐physiological system (hsMPS) with physiologically relevant gastric mucosal defense system is described based on the combination of organoid and MPS technology. A fluid flow enhanced epithelial‐mesenchymal interaction in the hsMPS enables functional maturation of gastric epithelial cells, which allows for the recreation of mesh‐like mucus layer containing high level of mucus protective peptides and well‐developed epithelial junctional complexes. Furthermore, gastroprotection mechanisms against Helicobacter pylori (H. pylori) are successfully demonstrated in this system. Therefore, hsMPS represents a new in vitro tool for research where gastric mucosal defense mechanism is pivotal for developing therapeutic strategies.

TLR3 plays a crucial role in anti-viral immune response by recognizing RNAs produced during virus infection. Here, the authors determine a high resolution structure of the activated cluster of TLR3. This structure will provide a platform for designing antiviral therapeutics and vaccines.

IntroductionIt is known that biological risk factors and lifestyle behaviors are important determinants of dementia. However, there has been yet to be sufficient evidence to prove that community-level social capital is one of the determinants of dementia. This retrospective cohort study is a large, long-term, population-based study that investigated the association between community-level social trust and the risk of dementia in the Republic of Korea.MethodsData came from the Korean National Health Insurance Service database. The community-level social trust values were determined by the Korean Community Health Survey. The study population consisted of 1,974,944 participants over 50 years of age and was followed up from 1 January 2012 to 31 December 2019 with a latent period of 5 years from 1 January 2012 to 31 December 2016. Cox proportional hazards regression was utilized to obtain the adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for the risk of dementia according to social trust quintiles.ResultsParticipants within the highest quintile of community-level social trust had a lower risk for overall dementia (aHR, 0.90; 95% CI, 0.86–0.94) and Alzheimer's disease (aHR, 0.90; 95% CI, 0.85–0.94) compared to those within the lowest quintile of community-level social trust. The alleviating trend association of high community-level social trust on dementia risk was maintained regardless of whether the participants had health examinations.ConclusionsOur findings suggest that higher community-level social trust is associated with a reduced risk of dementia. Community-level social trust is a crucial indicator of dementia and improving community-level social trust may lead to a lower risk of dementia.

Background/Aims We investigated the distribution of serum uric acid (SUA) levels and estimated the prevalence of hyperuricemia and hypouricemia in the Korean population. Methods This cross-sectional study used data from the Korean Genome and Epidemiology Study and included 172,970 participants (58,981 men and 113,989 women) aged 40 to 79 years. Hypouricemia and hyperuricemia were defined as SUA level ≤ 2.0 mg/dL and > 7 mg/dL, respectively. The prevalence of hyperuricemia and hypouricemia was evaluated by age and sex. Results The mean SUA levels were significantly higher in men than in women (5.71 ± 1.27 mg/dL vs. 4.21 ± 0.96 mg/dL, p < 0.001). The mean SUA levels and prevalence of hyperuricemia increased with age in women but not in men. The overall prevalence of hyperuricemia and that in men and women was 50.82, 133.25, and 8.17 per 1,000 persons, respectively; the overall prevalence of hypouricemia and that in men and women was 4.16, 1.10, and 5.75 per 1,000 persons, respectively. The prevalence of hypouricemia in men was similar across all age groups; however, that in women was the highest in the age group of 40 to 49 years and the lowest in the age group of 50 to 59 years. Conclusions The distribution of SUA levels and prevalence of hyperuricemia and hypouricemia differed according to age and sex. Age and sex should be considered in studies on uric acid-related diseases.

Early- and late-onset Alzheimer’s disease (AD) patients often exhibit distinct features. We sought to compare overall white matter connectivity and evaluate the pathological factors (amyloid, tau, and vascular pathologies) that affect the disruption of connectivity in these two groups. A total of 50 early- and 38 late-onset AD patients, as well as age-matched cognitively normal participants, were enrolled and underwent diffusion-weighted magnetic resonance imaging to construct fractional anisotropy-weighted white matter connectivity maps. [18F]-THK5351 PET, [18F]-Flutemetamol PET, and magnetic resonance imaging were used for the evaluation of tau and related astrogliosis, amyloid, and small vessel disease markers (lacunes and white matter hyperintensities). Cluster-based statistics was performed for connectivity comparisons and correlation analysis between connectivity disruption and the pathological markers. Both patient groups exhibited significantly disrupted connectivity compared to their control counterparts with distinct patterns. Only THK retention was related to connectivity disruption in early-onset AD patients, and this disruption showed correlations with most cognitive scores, while late-onset AD patients had disrupted connectivity correlated with amyloid deposition, white matter hyperintensities, and lacunes in which only a few cognitive scores showed associations. These findings suggest that the pathogenesis of connectivity disruption and its effects on cognition are distinct between EOAD and LOAD.

Abstract Background Foot involvement in rheumatoid arthritis (RA) patients has been reported to severely affect functional capacity and quality of life. We aimed to determine the impact of midfoot and hindfoot involvement on functional disability in Korean patients with RA. Methods We evaluated the RA involvement and deformity of three regions of the foot (forefoot, midfoot and hindfoot) and ankle using conventional radiography in Korean patients with RA. We compared the clinical features between RA patients with and without foot or ankle involvement. Using multivariable logistic regression analyses, the impact of midfoot or hindfoot involvement on functional disability in RA patients was evaluated. Results Overall, 120 patients with a median age of 48.0 [interquartile range (IQR), 37–56] years and median disease duration of 58.0 (IQR, 10–89) months were included. The prevalence of foot or ankle RA involvement was 74 (61.7%). The number of patients with forefoot, midfoot, hindfoot and ankle involvement was 32 (43.2%), 24 (32.4%), 46 (62.2%) and 4 (5.4%), respectively. Compared to patients without foot or ankle involvement those with such involvement had greater disease activity and functional disability, more of them were treated with biologic agents, and they had a lower health-related quality of life. After adjusting for potential confounders, hindfoot involvement was associated with a higher degree of functional disability. However, walking difficulty was more associated with midfoot involvement rather than with involvement in other regions. Conclusions In Korean patients with RA, hindfoot involvement is associated with functional disability and midfoot involvement affects walking.

Abstract Src homology 2 domain-containing protein tyrosine phosphatase 2 (SHP-2) is a cytoplasmic tyrosine phosphatase that is highly expressed in hematopoietic cells and in the CNS and exerts opposite effects on signal transduction by exerting a neuroprotective or proapoptotic effect. Several mutations of SHP-2 have been found in children with myeloproliferative disorders or malignant leukemia, and some of these can affect brain development. In the present study, we aimed to identify and functionally characterize genetic variations in SHP-2 in 72 preterm and 58 full-term infants and to evaluate the effect of the variations on neurodevelopment in preterm infants. Twelve genetic variations were identified. Among them, two variations in the SHP-2 promoter, g.-317C > T and g.-273G > A, were found to significantly increase promoter activity, and the frequency of g.-273G > A was higher in preterm infants than in full-term infants. Two transcription factors, NF-κB and GABPα, were found to be involved in the transcriptional regulation of SHP-2 by the two above-mentioned variations. In particular, we found that g.-273G > A was significantly associated with delayed myelination and poor motor development in preterm infants. Our results suggest that a functional promoter variation in SHP-2 is associated with spontaneous preterm birth itself as well as white matter myelination and neurodevelopment.

Alzheimer’s disease (AD) patients are known to have heterogeneous clinical presentation and pathologic patterns. We hypothesize that AD dementia can be categorized into subtypes based on multimodal imaging biomarkers such as magnetic resonance imaging (MRI), tau positron emission tomography (PET), and amyloid PET. We collected 3T MRI, 18F-THK5351 PET, and 18F-flutemetamol (FLUTE) PET data from 83 patients with AD dementia [Clinical Dementia Rating (CDR) ≤1] and 60 normal controls (NC), and applied surface-based analyses to measure cortical thickness, THK5351 standardized uptake value ratio (SUVR) and FLUTE SUVR for each participant. For the patient group, we performed an agglomerative hierarchical clustering analysis using the three multimodal imaging features on the vertices (n = 3 × 79,950). The identified AD subtypes were compared to NC using general linear models adjusting for age, sex, and years of education. We mapped the effect size within significant cortical regions reaching a corrected p-vertex

Adipose‐derived stem cells (ASCs) mainly exert their function by secreting materials that are collectively termed the secretome. Despite recent attention to the secretome as an alternative to stem cell therapy, the culture conditions for generating optimal secretome contents have not been determined. Therefore, we investigated the role of hypoxic‐conditioned media (HCM) from ASCs. Normoxic‐conditioned media (NCM) and HCM were obtained after culturing ASCs in 20% O2 or 1% O2 for 24 hours, respectively. Subsequently, partially hepatectomized mice were infused with saline, control medium, NCM, or HCM, and then sera and liver specimens were obtained for analyses. Hypoxia (1% O2) significantly increased mRNA expression of mediators from ASCs, including interleukin‐6 (IL‐6), tumor necrosis factor α (TNF‐α), hepatocyte growth factor (HGF), and vascular endothelial growth factor (VEGF). HCM infusion significantly increased the number of Ki67‐positive cells in the liver (p < .05). HCM infusion significantly increased phospho‐signal transducer and activator of transcription 3 (STAT3) and decreased suppressor of cytokine signaling 3 (SOCS3) expression in the liver (p < .05). To determine the role of IL‐6 in liver regeneration, we then performed IL‐6 RNA interference study. Conditioned media (CM) obtained from ASCs, which were transfected with either siIL‐6 or siControl, were administered to partially hepatectomized mice. The siIL‐6 CM groups exhibited lower liver proliferation (Ki67‐positive cells) and markers of regeneration (protein expression of proliferating cell nuclear antigen, p‐STAT3, HGF, and VEGF and liver weights) than the siControl CM groups (p < .05). Taken together, hypoxic preconditioning of ASCs increased expression of mediators promoting anti‐inflammatory and regenerative responses. The liver regenerative effects of HCM appear to be mediated by persistent and uninhibited expression of STAT3 in the liver, which results from decreased expression of SOCS3. Significance In this study, it was found that treatment with the medium from hypoxic‐preconditioned adipose‐derived stem cells (ASCs) increased the viability of hepatotoxic hepatocytes and enhance liver regeneration in partially hepatectomized mice. In addition, the researchers first revealed that the hepatoprotective effects of hypoxic‐conditioned media are mediated by persistent and uninhibited expression of signal transducer and activator of transcription 3 in the liver, which result from a decreased expression of suppressor of cytokine signaling 3. Therefore, the hypoxic preconditioning of ASCs is expected to play a crucial role in regenerative medicine by optimizing the production of a highly effective secretome from ASCs.

Signal Amplification by Reversible Exchange (SABRE), a hyperpolarization technique, has been harnessed as a powerful tool to achieve useful hyperpolarized materials by polarization transfer from parahydrogen. In this study, we systemically applied SABRE to a series of nitrile compounds, which have been rarely investigated. By performing SABRE in various magnetic fields and concentrations on nitrile compounds, we unveiled its hyperpolarization properties to maximize the spin polarization and its transfer to the next spins. Through this sequential study, we obtained a ~130-fold enhancement for several nitrile compounds, which is the highest number ever reported for the nitrile compounds. Our study revealed that the spin polarization on hydrogens decreases with longer distances from the nitrile group, and its maximum polarization is found to be approximately 70 G with 5 μL of substrates in all structures. Interestingly, more branched structures in the ligand showed less effective polarization transfer mechanisms than the structural isomers of butyronitrile and isobutyronitrile. These first systematic SABRE studies on a series of nitrile compounds will provide new opportunities for further research on the hyperpolarization of various useful nitrile materials.

BackgroundA low fraction of inspired oxygen (FiO2) increases venous deoxygenated hemoglobin concentrations, making the color of the blood darker. The present study was aimed to determine the effects of FiO2 on the ability to discriminate venous from arterial blood.MethodsOne-hundred and sixty surgical patients undergoing percutaneous central venous access of the internal jugular vein were randomly assigned to receive an FiO2 of 0.2, 0.4, 0.6, or 1.0 (n = 40 each) for at least 20 min prior to central line placement under general anesthesia. Vascular access was achieved with a 22-gauge needle; 2 ml of blood was withdrawn and shown to three physicians including the operator. Each of them was asked to identify the blood as 'arterial', 'venous' or 'not sure'. Simultaneous blood gas analysis of the samples was performed on blood taken from the puncture site and the artery after visual comparison to confirm blood's origin and hemodynamic measurements.ResultsLowering FiO2 progressively increased venous deoxygenated hemoglobin concentrations (2.24 ± 1.12, 3.30 ± 1.08, 3.66 ± 1.15, and 3.71 ± 1.33 g/dl) in groups having an FiO2 of 1.0, 0.6, 0.4 and 0.2, respectively (P < 0.001), thereby facilitating the 'venous' blood identification (P < 0.001). Neither heart rate nor mean arterial pressure differed among the groups. None developed hypoxemia (percutaneous hemoglobin oxygen saturation < 90%) in any group during the study period.ConclusionsA low FiO2 increases venous deoxygenated hemoglobin levels, thereby facilitating the recognition by clinicians of its venous origin in percutaneous central venous catheterization under general anesthesia.

The post-annealing mechanical behavior of 316L austenitic stainless steel (SUS316L) after electrically assisted (EA) annealing with a single pulse of electric current is experimentally investigated to evaluate the feasibility of a two-stage forming process of the selected SUS316L with rapid EA annealing. A tensile specimen is deformed to a specific prestrain and then annealed by applying a single pulse of electric current with a short duration less than 1 s. Finally, the specimen is reloaded until fracture. The stress-strain curve during reloading shows that the flow stress of the SUS316L significantly decreases, which indicates the occurrence of EA annealing. The electric current also increases the maximum achievable elongation of the SUS316L during reloading. The stress-strain curve during reloading and the microstructural observation suggest that the effects of EA annealing on the post-annealing mechanical behavior and microstructure strongly depend on both the applied electric current density (electric current per unit cross-sectional area) and the given prestrain. The results of the present study suggest that the EA annealing technique could be effectively used to improve the formability of SUS316L when manufacturing complex parts.