Lipid biosynthesis is recently studied its functions in a range of cellular physiology including differentiation and regeneration. However, it still remains to be elucidated in its precise function. ...To reveal this, we evaluated the roles of lysophosphatidic acid (LPA) signaling in alveolar bone formation using the LPA type 2 receptor (LPAR2) antagonist AMG‐35 (Amgen Compound 35) using tooth loss without periodontal disease model which would be caused by trauma and usually requires a dental implant to restore masticatory function. In this study, in vitro cell culture experiments in osteoblasts and periodontal ligament fibroblasts revealed cell type‐specific responses, with AMG‐35 modulating osteogenic differentiation in osteoblasts in vitro. To confirm the in vivo results, we employed a mouse model of tooth loss without periodontal disease. Five to 10 days after tooth extraction, AMG‐35 facilitated bone formation in the tooth root socket as measured by immunohistochemistry for differentiation markers KI67, Osteocalcin, Periostin, RUNX2, transforming growth factor beta 1 (TGF‐β1) and SMAD2/3. The increased expression and the localization of these proteins suggest that AMG‐35 elicits osteoblast differentiation through TGF‐β1 and SMAD2/3 signaling. These results indicate that LPAR2/TGF‐β1/SMAD2/3 represents a new signaling pathway in alveolar bone formation and that local application of AMG‐35 in traumatic tooth loss can be used to facilitate bone regeneration and healing for further clinical treatment.
We explored clinical implications of the new definition of metabolic dysfunction-associated steatotic liver disease (MASLD) by assessing its prevalence and associated cardiovascular disease (CVD) ...risk.
From nationwide health screening data, we identified 9 775 066 adults aged 20-79 who underwent health examination in 2009. Participants were categorised into four mutually exclusive groups: (1) MASLD; (2) MASLD with increased alcohol intake (MetALD); (3) MASLD with other combined aetiology (the three collectively referred to as MASLD/related steatotic liver disease (SLD)); and (4) no MASLD/related SLD. SLD was determined by fatty liver index ≥30. The primary outcome was CVD event, defined as a composite of myocardial infarction, ischaemic stroke, heart failure or cardiovascular death.
The prevalence of MASLD, MetALD and MASLD with other combined aetiology was 27.5%, 4.4% and 1.5%, respectively. A total of 8 808 494 participants without prior CVD were followed up for a median of 12.3 years, during which 272 863 CVD events occurred. The cumulative incidence and multivariable-adjusted risk of CVD were higher in participants with MASLD/related SLD than in those without (HR 1.38 (95% CI 1.37 to 1.39)). Multivariable-adjusted HR (95% CI) of CVD events was 1.39 (1.38 to 1.40) for MASLD, 1.28 (1.26 to 1.30) for MetALD and 1.30 (1.26 to 1.34) for MASLD with other combined aetiology compared to the absence of any of these conditions. CVD risk was also higher in participants with metabolic dysfunction-associated fatty liver disease or non-alcoholic fatty liver disease than in those without the respective condition.
Over one-third of Korean adults have MASLD/related SLD and bear a high CVD risk.
Background Understanding the mechanism behind immune cell plasticity in cancer metastasis is crucial for identifying key regulators. Previously we found that mitotic factors regulate ...epithelial-mesenchymal transition, but how these factors convert to metastatic players in the tumor microenvironment (TME) is not fully understood. Methods The clinical importance of mitotic factors was analyzed by heatmap analysis, a KM plot, and immunohistochemistry in lung adenocarcinoma (LUAD) patients. Immunoprecipitation, LC-MS/MS, kinase assay, and site-directed mutagenesis were performed for the interaction and phosphorylation. A tail-vein injection mouse model, Transwell-based 3D culture, microarray analysis, coculture with monocytes, and chromatin immunoprecipitation assays were used to elucidate the function of phosphorylated FoxM1 in metastasis of TME. Results The phosphorylated FoxM1 at Ser25 by PLK1 acquires the reprogramming ability to stimulate the invasive traits in cancer and influence immune cell plasticity. This invasive form of p-FoxM1 upregulates the expression of IL1A/1B, VEGFA, and IL6 by direct activation, recruiting monocytes and promoting the polarization of M2d-like tumor-associated macrophages (TAMs). Upregulation of PD-L1 in LUAD having phosphomimetic FoxM1 facilitates immune evasion. In invasive LUAD with phosphomimetic FoxM1, IFITM1 is the most highly expressed through the activation of the STING-TBK1-IRF3 signaling, which enhances FoxM1-mediated signaling. Clinically, higher expression of FOXM1, PLK1, and IFITM1 is inversely correlated with the survival rate of advanced LUAD patients, providing a promising therapeutic strategy for the treatment of LUAD. Conclusion FoxM1-based therapy would be a potential therapeutic strategy for LUAD to reduce TAM polarization, immune escape, and metastasis, since FoxM1 functions as a genetic reprogramming factor reinforcing LUAD malignancy in the TME. Keywords: FoxM1, Phosphorylation, PLK1, Invasiveness, Tumor-associated macrophages
Recent studies have shown that gestational diabetes mellitus (GDM) is associated with an increased risk for cardiovascular disease. GDM has also been shown to be a risk factor for type 2 diabetes ...(T2DM) after pregnancy. However, there is limited evidence regarding the role of intercurrent T2DM on the relationship between GDM and future CVD. Thus, we investigated the risks of incident cardiovascular events among women with GDM during pregnancy compared to women without GDM and whether the increased CVD risk is dependent on intercurrent development of T2DM. We conducted a population-based retrospective cohort study using the Korean National Health Insurance Service claims database. Outcomes were the first occurrence of any CVD (myocardial infarction, treatment with coronary revascularization, heart failure, and cerebrovascular disease). Cox proportional hazard models were used to assess the association between GDM and incident CVD events, using landmark analysis at 4 years. A total of 1,500,168 parous women were included in the analysis, of which 159,066 (10.60%) had GDM. At a median follow-up of 12.8 years, 13,222 incident cases of total CVD were observed. Multivariable-adjusted hazard ratio for total CVD among women with prior GDM, compared with those without GDM, was 1.08 (95% CI 1.02-1.14). Further classifying GDM by progression to T2DM in relation to total CVD risk indicated a positive association for GDM with progression to T2DM vs no GDM or T2DM (HR 1.74; 95% CI 1.40-2.15), and no statistically significant association for GDM only (HR 1.06; 95% CI 1.00-1.12). GDM with subsequent progression to T2DM were linked with an increased risk of cardiovascular diseases. These findings highlight the need for more vigilant postpartum screening for diabetes and the implementation of diabetes interventions in women with a history of GDM to reduce future CVD risk.
The association between nonalcoholic fatty liver disease (NAFLD) and colorectal cancer (CRC) has been controversial. Using the new consensus-driven definition, we evaluated the association of ...metabolic dysfunction-associated fatty liver disease (MAFLD) with the risk of developing CRC.
From a nationwide health screening database, we included 8,933,017 participants (48.6% male) aged 40-64 years between 2009 and 2010. Participants were categorized by the presence of fatty liver disease (FLD)-NAFLD and MAFLD, separately-and by the combination of the 2 definitions: neither FLD, NAFLD only, MAFLD only, or both FLD. The primary outcome was the development of CRC.
Among the participants, 2,517,330 (28.2%) had NAFLD, and 3,337,122 (37.4%) had MAFLD, whereas 2,465,151 (27.6%) met both NAFLD and MAFLD definitions. Over a median follow-up period of 10.1 years, 60,888 new CRC cases developed. NAFLD and MAFLD were each associated with a significantly higher risk of developing CRC. When the neither FLD group was the reference, multivariable-adjusted hazard ratios (95% confidence interval) for CRC were 1.16 (1.06-1.28) in the NAFLD only group, 1.18 (1.16-1.20) in the both FLD group, and 1.32 (1.28-1.35) in the MAFLD only group. The presence of advanced liver fibrosis further increased CRC risk in each FLD group.
FLD was associated with a higher risk of CRC development. CRC risk was higher in the presence of MAFLD, especially when accompanied by liver fibrosis.
This letter presents an efficiency analysis of a magnetic resonance wireless power transfer (WPT) system with an intermediate resonant coil. A helical coil and a spiral coil with an additional ...capacitor are considered as resonant coils for the WPT system. The intermediate resonant coil is set up coaxially and perpendicular to both the Tx and Rx resonant coils in order to observe the efficiency change according to the directions. The power efficiency is calculated using the temporal coupled mode theory (CMT). Impedance matching conditions are also shown by using the CMT. Analysis results show that using an intermediate coil properly improves efficiency and extends the distance between the transmitter and receiver. Both calculated and measured efficiencies are in good agreement. It is also shown that the intermediate resonant system has a good efficiency and is superior to nonintermediate systems.
PurposeThe National Health Insurance Service-Health Screening Cohort (NHIS-HEALS) is a cohort of participants who participated in health screening programmes provided by the NHIS in the Republic of ...Korea. The NHIS constructed the NHIS-HEALS cohort database in 2015. The purpose of this cohort is to offer relevant and useful data for health researchers, especially in the field of non-communicable diseases and health risk factors, and policy-maker.ParticipantsTo construct the NHIS-HEALS database, a sample cohort was first selected from the 2002 and 2003 health screening participants, who were aged between 40 and 79 in 2002 and followed up through 2013. This cohort included 514 866 health screening participants who comprised a random selection of 10% of all health screening participants in 2002 and 2003.Findings to dateThe age-standardised prevalence of anaemia, diabetes mellitus, hypertension, obesity, hypercholesterolaemia and abnormal urine protein were 9.8%, 8.2%, 35.6%, 2.7%, 14.2% and 2.0%, respectively. The age-standardised mortality rate for the first 2 years (through 2004) was 442.0 per 100 000 person-years, while the rate for 10 years (through 2012) was 865.9 per 100 000 person-years. The most common cause of death was malignant neoplasm in both sexes (364.1 per 100 000 person-years for men, 128.3 per 100 000 person-years for women).Future plansThis database can be used to study the risk factors of non-communicable diseases and dental health problems, which are important health issues that have not yet been fully investigated. The cohort will be maintained and continuously updated by the NHIS.
This study introduces a new flexible cathode that contains no binder, conductive additive and current collector, but instead consists solely of a sulfurized polyacrylonitrile nanofiber (SPAN) web ...which is prepared by a simple pyrolysis process with low cost raw materials. This not only exhibits good electrochemical properties, but also a high flexibility, rollability, and bendability to 180° without fracture. Its feasibility as a cathode for a low cost and flexible Na/S battery is subsequently evaluated on the basis that S, PAN, and Na are cheap materials. The SPAN web delivers a high first discharge capacity of 604 mAh g−1 – electrode (1473 mAh g−1 – sulfur) at 0.01 C based on sulfur content. In cycle performance at 0.1 C, a first discharge capacity of 342 mAh g−1 – electrode is obtained and remains over 266 mAh g−1 – electrode after 200 cycles along with the coulombic efficiency near 100% from the second cycle. In terms of rate capability, it is shown to be capable of delivering a capacity of as high as 71 mAh g−1 at 1 C. The reversible electrochemical reaction of the SPAN web with Na is related to a reversible bond between the C–S and S–S bonds of the SPAN web.
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•A flexible sulfurized polyacrylonitrile cathode was prepared by simple pyrolysis.•The SPAN cathode shows rollability, and bendability to 180° without fracture.•The cathode contains no binder, current collector and conducting additives.•Na/SPAN cell shows good cycle performance.•The 1st capacity of 342 mAh gelectrode−1 remains 266 mAh g−1 after 200 cycles.
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