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BACKGROUND: Recent genome-wide association studies (GWASs) in liver diseases have generated some polygenic risk scores (PRSs), but their predictive effectiveness on hepatocellular carcinoma (HCC) risk assessment remains unclear. METHODS: Here, we constructed a novel combined polygenic risk score and evaluated its increment to the well-established risk model. We used 15 HCC-associated genetic loci from two PRSs and FinnGen GWAS data to calculate a PRS-combined score and to fit the related PRS model in the UK Biobank cohort (N = 436,162). The PRS-combined score was further assessed for risk stratification for HCC integrating with the recommended clinical risk scores. RESULTS: The PRS-combined model achieved a better AUC (0.657) than that of PRS-HFC (0.637) and PRS-cirrhosis (0.645). The top 20% of the PRS-combined distribution had a 3.25 increased risk of HCC vs. the middle decile (45-55%). At the population level, the addition of PRS-combined to the CLivD score significantly increased the C-statistic (from 0.716 to 0.746) and provided a remarkable improvement in reclassification (NRI = 0.088) at the 10-year risk threshold of 0.2%. In clinic, additional assessment of PRS-combined would reclassify 34,647 intermediate-risk participants as high genetic risk, corresponding to an increase of 63.92% (62/97) of the HCC events classified at high risk using the Fibrosis-4 alone. CONCLUSIONS: The PRS may enhance HCC risk prediction effectiveness in the general population and refine risk stratification of the conventional clinical indicator.
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Rehmannia piasezkii is a kind of medicinal plants, of the Orobanchaceae family, and well known for its large pink or purple corolla. However, no research on the molecular mechanism of flower color formation in R. piasezkii has been conducted so far. In this study, we investigated the transcriptome of root, stem, leaf and corollas of R. piasezkii using transcriptome sequencing technology and assembled 144,582 unigenes. A total of 58 anthocyanin biosynthetic genes were identified in the R. piasezkii transcriptome, fourteen of which were highly correlated with anthocyanin content, especially RpF3H2, RpDFR2, RpANS1, RpANS2 and RpUFGT. Totally, 35 MYB genes with FPKM values greater than 5 were identified in the R. piasezkii transcriptome, including an R2R3 MYB transcriptional factor RpMYB1, which belongs to subgroup 6 of the R2R3 MYB family. Agrobacterium-mediated transient expression of Nicotiana benthamiana revealed that overexpression of RpMYB1 could activate the expression of structural genes in anthocyanin synthesis pathway and promote the accumulation of anthocyanins in N. benthamiana leaves, indicating that RpMYB1 is a positive regulator of anthocyanin synthesis. Furthermore, combined transient overexpression of RpMYB1 with RpANS1, RpMYB1+RpANS1 with other structural genes all could further enhance the accumulation of anthocyanins in N. benthamiana leaves. Permanent overexpression of RpMYB1 in R. glutinosa promoted anthocyanin accumulation and expression levels of RgCHS, RgF3H, RgDFR and RgANS. Further evidence from dual-luciferase assay suggested that RpMYB1 could bind to the promoter of RpDFR2 and hence activating its expression. These findings provide insight into the molecular regulation in anthocyanin biosynthesis in R. piasezkii and provide valuable genetic resources for the genetic improvement of flower color.
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Background and Aims: Age-related mosaic chromosomal alterations (mCAs) detected from genotyping of blood-derived DNA are structural somatic variants that indicate clonal hematopoiesis. This study aimed to investigate whether mCAs contribute to the risk of cirrhosis and modify the effect of a polygenic risk score (PRS) on cirrhosis risk prediction. Methods: mCA call sets of individuals with European ancestry were obtained from the UK Biobank. The PRS was constructed based on 12 susceptible single-nucleotide polymorphisms for cirrhosis. Cox proportional hazard models were applied to evaluate the associations between mCAs and cirrhosis risk. Results: Among 448,645 individuals with a median follow-up of 12.5 years, we identified 2,681 cases of cirrhosis, 1,775 cases of compensated cirrhosis, and 1,706 cases of decompensated cirrhosis. Compared to non-carriers, individuals with copy-neutral loss of heterozygosity mCAs had a significantly increased risk of cirrhosis (hazard ratio (HR) 1.42, 95% confidence interval (CI) 1.12-1.81). This risk was higher in patients with expanded cell fractions of mCAs (cell fractions ≥10% vs. cell fractions <10%), especially for the risk of decompensated cirrhosis (HR 2.03 [95% CI 1.09-3.78] vs. 1.14 [0.80-1.64]). In comparison to non-carriers of mCAs with low genetic risk, individuals with expanded copy-neutral loss of heterozygosity and high genetic risk showed the highest cirrhosis risk (HR 5.39 [95% CI 2.41-12.07]). Conclusions: The presence of mCAs is associated with increased susceptibility to cirrhosis risk and could be combined with PRS for personalized cirrhosis risk stratification.
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Temperature can reflect vital activities, and researchers have attempted to guide Chinese medicine diagnosis and treatment by observing acupoint temperature changes. Integrating a temperature sensor at the needle tip enables in situ acupoint temperature measurement. However, the sensor needles for acupoint temperature monitoring designed in previous studies were fabricated by manually soldering thermistor beads and metal wires, making mass production difficult. In this work, using MEMS manufacturing technology, a flexible temperature sensor that can be integrated at the needle tip is proposed and can be mass-produced on silicon wafers. The sensor uses a Pt thermistor as the temperature-sensing element and has a slender flexible structure with dimensions of 125 µm width by 3.2 cm length. As the sensor is inserted into a hollow needle, the Pt thermistor is glued to the needle tip. In the temperature range of 30 °C to 50 °C, the fabricated temperature sensor has a sensitivity of 5.00 Ωâ°C-1, a nonlinearity of ±0.39%FS, and a repeatability error of ±2.62%FS. Additionally, the sensor has been applied to in vivo acupoint temperature monitoring experiments in rats and demonstrated good performance, suggesting its promise for future research on acupoint temperature.
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BACKGROUND: Buyang Huanwu Decoction (BHD) is widely used in Chinese clinical practice for the treatment and prevention of ischemic cerebral vascular diseases. This study was designed to investigate the effects of BHD on ischemic stroke (IS) and its underlying mechanism. METHODS: The middle cerebral artery occlusion (MCAO) rat model and oxygen-glucose deprivation and reoxygenation (OGD/R) rat brain microvascular endothelial cell (RBMVEC) models were established. Brain infarction size and neurological score were calculated following MCAO surgery. Evans blue was used to measure blood brain barrier (BBB) permeability. Cell counting kit-8 (CCK-8) and TUNEL assays were performed to evaluate the cell viability and apoptosis of RBMVECs. Dual-luciferase reporter assay was used to analyze the transcriptional activities of apoptosis-related genes. RESULTS: Results showed that higher infarction volume, neurological scores, and BBB permeability in the MCAO group rats were reduced after BHD treatment. Drug serum (DS) treatment had no impact on the normal RBMVECs' cell viability and cell apoptosis. Besides, DS treatment decreased the lactate production, glucose uptake, and extracellular acidification rate in normal and OGD/R-induced RBMVECs. DS treatment downregulated the protein levels of pan-lysine lactylation (kla), histone H3 lysine 18 lactylation (H3K18la), and the transcriptional of apoptotic protease activating factor-1 (Apaf-1) in OGD/R-treated RBMVECs. In addition, Apaf-1 overexpression decreased cell viability and increased apoptosis and glycolysis activity of OGD/R-treated RBMVECs. CONCLUSION: In summary, BHD inhibited glycolysis and apoptosis via suppressing the pan-kla and H3K18la protein levels and the Apaf-1 transcriptional activity, thus restraining the progression of IS.
Subject(s)
Apoptosis , Drugs, Chinese Herbal , Endothelial Cells , Glycolysis , Ischemic Stroke , Rats, Sprague-Dawley , Animals , Drugs, Chinese Herbal/pharmacology , Apoptosis/drug effects , Endothelial Cells/drug effects , Endothelial Cells/metabolism , Glycolysis/drug effects , Ischemic Stroke/drug therapy , Ischemic Stroke/metabolism , Rats , Male , Brain/drug effects , Brain/metabolism , Blood-Brain Barrier/drug effects , Blood-Brain Barrier/metabolism , Cell Survival/drug effects , Infarction, Middle Cerebral Artery/drug therapy , Infarction, Middle Cerebral Artery/metabolism , Glucose/metabolism , Microvessels/drug effects , Microvessels/metabolism , Disease Models, AnimalABSTRACT
Rehmannia glutinosa is one of the commonly used Chinese herbal medicines, which has activities of heat-clearing,blood-cooling, Yin-nourishing, and body fluid-promoting. Iridoid glycosides are the main bioactive in R. glutinosa. Iridoid oxidase is a key rate-limiting enzyme in the biosynthetic pathway of iridoid glycosides. In this study, an iridoid oxidase gene Rg IO was screened based on the transcriptome data, followed by bioinformatics analysis, expression characteristic detection, and subcellular localization analysis. The results show that the coding region of Rg IO is 1 536 bp, with 511 amino acids encoded, and the molecular weight is about 58 258. 01. The protein sequence of Rg IO contains the conserved domains and motifs of cytochrome P450 oxidases. Rg IO has the highest sequence identities with its ortholog proteins in Striga asiatica, Striga hermonthica, and Centranthera grandiflora and has good sequence identities(77. 28%) with Catharanthus roseus Cr IO. Rg IO shows specific expression in the leaf of R. glutinosa. In response to MeJA induction, the expression of MeJA in leaves and roots after treatment increases by 3. 15 and 1. 3 times at 3 h and 6 h,respectively. The result of subcellular localization shows that Rg IO is distributed in the endoplasmic reticulum. Agrobacterium-mediated transient expression of Rg IO gene in leaves of R. glutinosa makes the content of catalpol increase by 0. 82 times compared with the transient expression of the empty vector. This study provides a key target gene for the molecular regulation and biosynthesis of catalpol in R. glutinosa and lays a foundation for revealing the complete biosynthetic pathway of catalpol.
Subject(s)
Cloning, Molecular , Plant Proteins , Rehmannia , Rehmannia/genetics , Rehmannia/enzymology , Rehmannia/chemistry , Plant Proteins/genetics , Plant Proteins/metabolism , Plant Proteins/chemistry , Gene Expression Regulation, Plant , Phylogeny , Amino Acid SequenceABSTRACT
Risk prediction tools for colorectal cancer (CRC) have potential to improve the efficiency of population-based screening by facilitating risk-adapted strategies. However, such an applicable tool has yet to be established in the Chinese population. In this study, a risk score was created using data from the China Kadoorie Biobank (CKB), a nationwide cohort study of 409,854 eligible participants. Diagnostic performance of the risk score was evaluated in an independent CRC screening programme, which included 91,575 participants who accepted colonoscopy at designed hospitals in Zhejiang Province, China. Over a median follow-up of 11.1 years, 3136 CRC cases were documented in the CKB. A risk score was created based on nine questionnaire-derived variables, showing moderate discrimination for 10-year CRC risk (C-statistic = 0.68, 95 % CI: 0.67-0.69). In the CRC screening programme, the detection rates of CRC were 0.25 %, 0.82 %, and 1.93 % in low-risk (score <6), intermediate-risk (score: 6-19), and high-risk (score >19) groups, respectively. The newly developed score exhibited a C-statistic of 0.65 (95 % CI: 0.63-0.66), surpassing the widely adopted tools such as the Asia-Pacific Colorectal Screening (APCS), modified APCS, and Korean Colorectal Screening scores (all C-statistics = 0.60). In conclusion, we developed a novel risk prediction tool that is useful to identify individuals at high risk of CRC. A user-friendly online calculator was also constructed to encourage broader adoption of the tool.
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Colonoscopy , Colorectal Neoplasms , Early Detection of Cancer , Humans , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/epidemiology , China/epidemiology , Male , Female , Early Detection of Cancer/methods , Middle Aged , Risk Assessment/methods , Aged , Colonoscopy/methods , Risk Factors , Mass Screening/methods , Cohort Studies , Surveys and QuestionnairesABSTRACT
Obtaining lignin-based graphite-like microcrystallites at a relatively low carbonization temperature is still very challenging. In this work, we report a new method based on condensed structures, for regulating graphite-like microcrystalline structures via the incorporation of 4,4'-diphenylmethane diisocyanate (MDI) into the main structure of lignin. The effects of MDI on the thermal properties of lignin and the graphite-like microcrystalline structure of lignin-based ultrafine carbon fibers were extensively studied and investigated. The incorporation of MDI decreased the thermal stability of lignin, increased the carbon yield and enhanced the formation of graphite-like microcrystallites, which are beneficial for reducing energy consumption during the preparation of lignin-based carbon fibers. The modified lignin-based ultrafine carbon fibers (M-LCFs) demonstrated satisfactory electrochemical performance, including high specific capacitance, low charge transfer resistance, and good cycle performance. The M-LCFs-3/2 electrode had a specific capacitance of 241.3â¯Fâ¯g-1 at a current density of 0.5 A g-1, and a residual ratio of 90.2â¯% after 2000 charge and discharge cycles. This study provides a new approach to control the graphite-like microcrystalline structure and electrochemical performance while also optimizing the temperature.
Subject(s)
Carbon Fiber , Graphite , Lignin , Lignin/chemistry , Graphite/chemistry , Carbon Fiber/chemistry , Crystallization , Temperature , Electric Capacitance , Electrodes , Carbon/chemistryABSTRACT
Topographic measurements of micro- or nanostructures are essential in cutting-edge scientific disciplines such as optical communications, metrology, and structural biology. Despite the advances in surface metrology, measuring micron-scale steps with wide field of view (FOV) and high-resolution remains difficult. This study demonstrates a dual-wavelength Fourier ptychographic microscopy for high-resolution topographic measurement across a wide FOV using an aperture scanning structure. This structure enables the capture of a three-dimensional (3D) sample's scattered field with two different wavelength lasers, thus allowing the axial measurement range growing from nano- to micro-scale with enhanced lateral resolution. To suppress the unavoidable noises and artifacts caused by temporal coherence, system vibration, etc., a total variation (TV) regularization algorithm is introduced for phase retrieval. A blazed grating with micron-scale steps is used as the sample to validate the performance of our method. The agreement between the high-resolution reconstructed topography with our method and that with atomic force microscopy verified the effectiveness. Meanwhile, numerical simulations suggest that the method has the potential to characterize samples with high aspect-ratio steps.
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INTRODUCTION: Insulin resistance (IR) plays an important role in the occurrence and development of cardiovascular disease (CVD) in patients with chronic kidney disease (CKD). The triglyceride-glucose (TyG) index is a simple and effective tool to evaluate IR. This study aimed to evaluate the association of the TyG index with coronary artery disease (CAD) and the severity of coronary artery stenosis (CAS) in nondialysis patients with stages 3-5 CKD. METHODS: Nondialysis patients with stages 3-5 CKD who underwent the first coronary angiography at Zhongda Hospital affiliated with Southeast University from August 2015 to January 2017 were retrospectively analyzed. CAS was measured by coronary angiography, and the CAS score was calculated as the Gensini score. Logistic regression analysis was used to determine the related factors of CAD and severe CAS. RESULTS: A total of 943 patients were enrolled in this cross-sectional study and 720 (76.4%) of these patients were diagnosed with CAD. The TyG index in the CAD group (7.29 ± 0.63) was significantly higher than that in the non-CAD group (7.11 ± 0.61) (p < 0.001). Multivariate logistic regression analysis showed that a higher TyG index was an independent risk factor for CAD in CKD patients after adjusting for related confounding factors (OR = 2.865, 95% CI 1.681-4.885, p < 0.001). Patients in the CAD group were divided into three groups according to the Gensini integral quantile level. Multivariate logistic regression analysis showed that the TyG index was an independent related factor for severe CAS after adjusting for relevant confounding factors (p < 0.001). CONCLUSIONS: The TyG index is associated with CAD and the severity of CAS in patients with nondialysis stages 3-5 CKD. A higher TyG index is an independent factor for CAD and severe CAS.
Subject(s)
Coronary Artery Disease , Coronary Stenosis , Renal Insufficiency, Chronic , Humans , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/epidemiology , Coronary Artery Disease/etiology , Glucose , Retrospective Studies , Triglycerides , Cross-Sectional Studies , Blood Glucose/analysis , Biomarkers , Coronary Stenosis/diagnostic imaging , Coronary Stenosis/etiology , Risk Factors , Renal Insufficiency, Chronic/complicationsABSTRACT
Wetlands serve many functions, including conserving water, providing habitats for animals and plants, and regulating climate change. Their unique ecological effects on the natural environment are indispensable in the whole ecosystem. Dianchi Lake Basin is located in Yunnan-Guizhou Plateau, China, and mainly in Kunming. It is a typical plateau urban wetland area. Based on spatio-temporal hotspot mining, spatio-temporal geographically weighted regression, and adaptive multidimensional grey prediction, we conducted correlation analyses of the wetland changes in Dianchi Lake Basin from 1993 to 2020 under the influence of human activities and natural conditions. The results show that (1) the active wetland change zone in Dianchi Lake Basin is mainly located around Dianchi Lake, and (2) the wetlands in some areas on the north and south of Dianchi Lake declined in the early 21st century, but under the protection policy in recent years, the wetlands in these areas gradually recovered. Meanwhile, the wetlands in most areas around Dianchi Lake showed a significant growth trend from 2018 to 2020. The results suggest that the wetland change in Dianchi Lake Basin is mainly related to the urbanization of Kunming, and it can be divided into five regions (strong negative correlation, weak negative correlation, weak correlation, weak positive correlation, and strong positive correlation) according to the different correlation of human activity intensity, among which the main factors affected by nature are different, but they are all related to temperature. This study shows that, although wetlands in plateau cities can be properly restored under proper protection, wetland protection should be kept in step with the development of plateau cities to support sustainable urban development and carbon neutrality.
Subject(s)
Ecosystem , Wetlands , Humans , Lakes , Environmental Monitoring/methods , ChinaABSTRACT
Abrasive water jet polishing has significant advantages in the manufacturing of complex optical components (such as high-slope optical component cavities) that require high-precision manufacturing. This is due to its processing process, in which the polishing tool does not make direct contact with the surface of the workpiece, and instead maintains a considerable distance. However, the removal functions of most existing abrasive water-jet polishing technologies do not possess strict symmetry, which significantly impacts the ability to correct surface figure errors. Therefore, this study implements rotating abrasive water-jet polishing based on traditional abrasive water jet processing to optimize the removal function, which turns it into a Gaussian form; thus, obtaining a type of removal function more suitable for CCOS polishing. This paper derives an empirical formula between the distance s' from the peak removal point of the removal function to the stagnation point and the nozzle tilt angle α, based on geometric relationships and experimental results, analyzes the relationship between material removal efficiency, nozzle tilt angle, and standoff distance. Finally, this paper verifies through experiments the validity of this empirical formula under different process parameters. Therefore, this study obtains the process conditions that allow rotating abrasive water-jet polishing technology to achieve a stable Gaussian form removal function, and the appropriate process parameters to be selected in conjunction with polishing efficiency; thereby, effectively improving the removal function's corrective ability and manufacturing efficiency. It provides theoretical support for the processing capability and process parameter selection of abrasive water-jet polishing technology, solves the problem of limited shaping capability of existing abrasive water jet tools, and significantly improves the manufacturing capability of high-end optical components.
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OBJECTIVE: China concentrates a large part of the global burden of HBV infection, playing a pivotal role in achieving the WHO 2030 global hepatitis elimination target. METHODS: We searched for studies reporting HBV surface antigen (HBsAg) seroprevalence in five databases until January 2023. Eligible data were pooled using a generalised linear mixed model with random effects to obtain summary HBsAg seroprevalence. Linear regression was used to estimate annual percentage change (APC) and HBsAg prevalence in 2021. RESULTS: 3740 studies, including 231 million subjects, were meta-analysed. HBsAg seroprevalence for the general population decreased from 9.6% (95% CI 8.4 to 10.9%) in 1973-1984 to 3.0% (95% CI 2.1 to 3.9%) in 2021 (APC=-3.77; p<0.0001). Decreases were more pronounced in children <5 years (APC=-7.72; p<0.0001) and 5-18 years (-7.58; p<0.0001), than in people aged 19-59 years (-2.44; p<0.0001), whereas HBsAg seroprevalence increased in persons ≥60 years (2.84; p=0.0007). Significant decreases were observed in all six major Chinese regions, in both men (APC=-3.90; p<0.0001) and women (-1.82; p<0.0001) and in high-risk populations. An estimated 43.3 million (95% uncertainty interval 30.7-55.9) persons remained infected with HBV in China in 2021 (3.0%), with notable heterogeneity by region (<1.5% in North China to>6% in Taiwan and Hong Kong) and age (0.3%, 1.0%, 4.7% and 5.6% for <5 years, 5-18 years, 19-59 years and ≥60 years, respectively). CONCLUSIONS: China has experienced remarkable decreases in HBV infection over the last four decades, but variations in HBsAg prevalence persist in subpopulations. Ongoing prevention of HBV transmission is needed to meet HBV elimination targets by 2030. TRIAL REGISTRATION NUMBER: PROSPERO (CRD42021284217).
Subject(s)
Hepatitis B, Chronic , Hepatitis B , Child , Male , Humans , Female , Hepatitis B, Chronic/epidemiology , Hepatitis B, Chronic/prevention & control , Hepatitis B Surface Antigens/analysis , Prevalence , Seroepidemiologic Studies , China/epidemiology , Hepatitis B virusABSTRACT
With the continuous development of modern optical systems, the demand for full spatial frequency errors of optical components in the system is increasing. Although computer-controlled sub-aperture polishing technology can quickly correct low-frequency errors, this technology significantly worsens the mid-frequency errors on the surface of the component, which greatly inhibits the improvement of optical system performance. Therefore, we conducted in-depth research on the non-stationary effect of the removal function caused by the fluctuation in magnetorheological polishing and their influence on the mid-frequency errors of the component surface. We established a non-stationary profile model of the removal function and applied this model to simulate the distribution of mid-frequency errors on the surface of the processed component, considering the non-stationary effect. The simulation results showed that the non-stationary effect of the removal function weaken the mid-frequency ripple errors but increase other mid-frequency errors. Therefore, we first proposed the optimal single-material removal thickness corresponding to the non-stationary effect and experimentally verified the effectiveness of the optimal material removal thickness in suppressing mid-frequency errors. The experimental results showed that when the magnetorheological finishing single-material removal thickness is set to the optimal value, both the mid-frequency ripple errors and the mid-frequency RMS on the surface significantly decrease. Therefore, this work provides a basis for improving the existing magnetorheological finishing process and effectively suppressing the mid-frequency errors on the surface of processed components. It also provides theoretical and technical support for the magnetorheological processing and manufacturing of high-precision optical components. At the same time, the non-stationary effect and the corresponding analytical models has the potential to be extended to other polishing tools.
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BACKGROUND AND AIMS: The hallmark of NAFLD or hepatic steatosis is characterized by lipid droplet (LD) accumulation in hepatocytes. Autophagy may have profound effects on lipid metabolism and innate immune response. However, how innate immune activation may regulate the autophagic degradation of intracellular LDs remains elusive. APPROACH AND RESULTS: A mouse model of a high-fat diet-induced NASH was used in the myeloid-specific stimulator of interferon genes (STING) knockout or STING/yes-associated protein (YAP) double knockout mice. Liver injury, lipid accumulation, lipid droplet proteins, autophagic genes, chromatin immunoprecipitation coupled with massively parallel sequencing, and RNA-Seq were assessed in vivo and in vitro . We found that high-fat diet-induced oxidative stress activates STING and YAP pathways in hepatic macrophages. The acrophage STING deficiency (myeloid-specific STING knockout) enhances nuclear YAP activity, reduces lipid accumulation, and increases autophagy-related proteins ATG5, ATG7, and light chain 3B but diminishes LD protein perilipin 2 expression. However, disruption of STING and YAP (myeloid STING and YAP double knockout) increases serum alanine aminotransferase and triglyceride levels and reduces ß-fatty acid oxidation gene expression but augments perilipin 2 levels, exacerbating high-fat diet-induced lipid deposition. Chromatin immunoprecipitation coupled with massively parallel sequencing reveals that macrophage YAP targets transmembrane protein 205 and activates AMP-activated protein kinase α, which interacts with hepatocyte mitofusin 2 and induces protein disulfide isomerase activation. Protein disulfide isomerase activates hypoxia-inducible factor-1α signaling, increases autophagosome colocalization with LDs, and promotes the degradation of perilipin 2 by interacting with chaperone-mediated autophagy chaperone HSC70. CONCLUSIONS: The macrophage STING-YAP axis controls hepatic steatosis by reprogramming lipid metabolism in a transmembrane protein 205/mitofusin 2/protein disulfide isomerase-dependent pathway. These findings highlight the regulatory mechanism of the macrophage STING-driven YAP activity on lipid control.
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BACKGROUND: The role of genetic background underlying the disparity of relative risk of smoking and lung cancer between European populations and East Asians remains unclear. METHODS: To assess the role of ethnic differences in genetic factors associated with smoking-related risk of lung cancer, we first constructed ethnic-specific polygenic risk scores (PRSs) to quantify individual genetic risk of lung cancer in Chinese and European populations. Then, we compared genetic risk and smoking as well as their interactions on lung cancer between two cohorts, including the China Kadoorie Biobank (CKB) and the UK Biobank (UKB). We also evaluated the absolute risk reduction over a 5-year period. RESULTS: Differences in compositions and association effects were observed between the Chinese-specific PRSs and European-specific PRSs, especially for smoking-related loci. The PRSs were consistently associated with lung cancer risk, but stronger associations were observed in smokers of the UKB [hazard ratio (HR) 1.26 vs 1.15, P = 0.028]. A significant interaction between genetic risk and smoking on lung cancer was observed in the UKB (RERI, 11.39 (95% CI, 7.01-17.94)], but not in the CKB. Obvious higher absolute risk was observed in nonsmokers of the CKB, and a greater absolute risk reduction was found in the UKB (10.95 vs 7.12 per 1000 person-years, P <0.001) by comparing heavy smokers with nonsmokers, especially for those at high genetic risk. CONCLUSIONS: Ethnic differences in genetic factors and the high incidence of lung cancer in nonsmokers of East Asian ethnicity were involved in the disparity of smoking-related risk of lung cancer.
Subject(s)
Lung Neoplasms , Humans , Lung Neoplasms/epidemiology , Lung Neoplasms/genetics , Prospective Studies , Smoking/adverse effects , Smoking/genetics , Risk Factors , Tobacco Smoking , Genetic Risk ScoreABSTRACT
Background and Aims: The recently proposed concept of metabolic dysfunction-associated fatty liver disease (MAFLD) has remained controversial. We aimed to describe the features and associated outcomes to examine the diagnostic ability of MAFLD for identifying high-risk individuals. Methods: In this retrospective cohort study, we enrolled 72,392 Chinese participants between 2014 and 2015. Participants were classified as MAFLD, nonalcoholic fatty liver disease (NAFLD), non-MAFLD-NAFLD, and a normal control group. The primary outcomes were liver-related and cardiovascular disease (CVD) events. Person-years of follow-up were calculated from enrolment to the diagnosis of the event, or the last date of data (June, 2020). Results: Of the 72,392 participants, 31.54% (22,835) and 28.33% (20,507) qualified the criteria for NAFLD or MAFLD, respectively. Compared with NAFLD, MAFLD patients were more likely to be male, overweight, and have higher biochemical indices including liver enzyme levels. Lean MAFLD diagnosed with ≥2 or ≥3 metabolic abnormalities presented similar clinical manifestations. During the median follow-up of 5.22 years, 919 incident cases of severe liver disease and 2,073 CVD cases were recorded. Compared with the normal control group, the NAFLD and MAFLD groups had a higher cumulative risk of liver failure and cardiac-cerebral vascular diseases. There were no significant differences in risk between the non-MAFLD-NAFLD and normal group. Diabetes-MAFLD group had the highest incidence of liver-related and cardiac-cerebral vascular diseases, lean MAFLD came second, and obese-MAFLD had the lowest incidence. Conclusions: This real-world study provided evidence for rationally assessing the benefit and practicability of the change in terminology from NAFLD to MAFLD. MAFLD may be better than NAFLD in identifying fatty liver with worse clinical features and risk profile.
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Fused silica has become the preferred optical material in the field of inertial confinement fusion (ICF) due to its excellent performance; however, these costly optical elements are vulnerable, and their manufacture is time-consuming. Therefore, the restoration of laser-induced damage for these optical elements is of great value. To restrain the post-restoration raised rim problem in the CO2 laser repair process to improve the restoration quality, the separate influences of key parameters of laser power, irradiation duration, and laser beam diameter on post-restoration pit morphology are compared in combined simulation and experimental studies. An optimized, patterned CO2 laser strategy is proposed and verified; the results indicate that, with the strategy, the rim height decreases from 2.6 µm to 1.52 µm, and maximal photo thermal absorption is decreased from 784.2 PPM to 209.43 PPM.
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Background: The Körperkoordinationstest Für Kinder (KTK) is a reliable and low-cost motor coordination test tool that has been used in several countries. However, whether the KTK is a reliable and valid instrument for use in Chinese children has not been assessed. Additionally, because the KTK was designed to incorporate locomotor, object control, and stability skills, and there is a lack of measurement tools that include stability skills assessment for Chinese children, the KTK's value and validity are worth discussing. Methods: A total of 249 primary school children (131 boys; 118 girls) aged 9-10 years from Shanghai were recruited in this study. Against the Test of Gross Motor Development-3 (TGMD-3), the concurrent validity of the KTK was assessed. We also tested the retest reliability and internal consistency of the KTK. Results: The test-retest reliability of the KTK was excellent (overall: r = 0.951; balancing backwards: r = 0.869; hopping for height: r = 0.918; jumping sideways: r = 0.877; moving sideways: r = 0.647). Except for the boys, the internal consistency of the KTK was higher than the acceptable level of Cronbach's α > 0.60 (overall: α = 0.618; boys: α = 0.583; girls: α = 0.664). Acceptable concurrent validity was found between the total scores for the KTK and TGMD-3 (overall: r = 0.420, p < 0.001; boys: r = 0.411, p < 0.001; girls: r = 0.437, p < 0.001). Discussion: The KTK is a reliable instrument for assessing the motor coordination of children in China. As such, the KTK can be used to monitor the level of motor coordination in Chinese children.