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BACKGROUND: Psoriasis is a chronic inflammatory disease that causes significant disability. However, little is known about the underlying metabolic mechanisms of psoriasis. Our study aims to investigate the causality of 975 blood metabolites with the risk of psoriasis. MATERIALS AND METHODS: We mainly applied genetic analysis to explore the possible associations between 975 blood metabolites and psoriasis. The inverse variance weighted (IVW) method was used as the primary analysis to assess the possible association of blood metabolites with psoriasis. Moreover, generalized summary-data-based Mendelian randomization (GSMR) was used as a supplementary analysis. In addition, linkage disequilibrium score regression (LDSC) was used to investigate their genetic correction further. Metabolic pathway analysis of the most suggested metabolites was also performed using MetaboAnalyst 5.0. RESULTS: In our primary analysis, 17 metabolites, including unsaturated fatty acids, phospholipids, and triglycerides traits, were selected as potential factors in psoriasis, with odd ratios (OR) ranging from 0.986 to 1.01. The GSMR method confirmed the above results (ß = 0.001, p < 0.05). LDSC analysis mainly suggested the genetic correlation of psoriasis with genetic correlations (rg) from 0.088 to 0.155. Based on the selected metabolites, metabolic pathway analysis suggested seven metabolic pathways including ketone body that may be prominent pathways for metabolites in psoriasis. CONCLUSION: Our study supports the causal role of unsaturated fatty acid properties and lipid traits with psoriasis. These properties may be regulated by the ketone body metabolic pathway.
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Análise da Randomização Mendeliana , Psoríase , Psoríase/sangue , Psoríase/genética , Psoríase/metabolismo , Humanos , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único , Desequilíbrio de Ligação , Metaboloma/fisiologia , Metaboloma/genética , Redes e Vias Metabólicas/genéticaRESUMO
To satisfy the demands of photodetectors for weak-light detection, materials selected for device fabrication should have an extremely low background carrier concentration to suppress the dark current of devices. In this work, a new quasi-two-dimensional CsGaGeSe4 single crystal with an extremely low background carrier concentration was synthesized by a co-solvent reaction based on which a photoconductive detector was prepared with an ultralow dark current density (6 fA at 1 V and â¼10-10 A cm-2) and a high response speed (â¼0.74 s) was achieved, presenting a great potential of being applied to the field of weak-light detection. The ultralow dark current density originates from both the good crystal quality and the strongly asymmetric band structure of CsGaGeSe4. In the darkness, electrons locally bound in the valence band bring an ultralow dark current density; after illumination, the electrons transiting to the conduction band will participate in the conduction in a non-localized state, resulting in a high signal-to-noise ratio. This work not only provides a new choice of potential materials for weak-light detection but also proposes an effective strategy for material selection.
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The liver plays a key role in keeping the homeostasis of glucose and lipid metabolism. Insulin resistance of the liver induced by extra glucose and lipid ingestion contributes greatly to chronic metabolic disease, which is greatly threatening to human health. The small peptide, VLPVPQK, originating from casein hydrolysates of milk, shows various health-promoting functions. However, the effects of VLPVPQK on metabolic disorders of the liver are still not fully understood. Therefore, in the present study, the effects and regulatory mechanism of VLPVPQK on insulin-resistant HepG2 cells was further investigated. The results showed that VLPVPQK exerted strong scavenging capacities against various free radicals, including oxygen radicals, hydroxyl radicals, and cellular reactive oxygen species. In addition, supplementation of VLPVPQK (62.5, 125, and 250 µM) significantly reversed the high glucose and fat (30 mM glucose and 0.2 mM palmitic acid) induced decrement of glucose uptake in HepG2 cells without affecting cell viability. Furthermore, VLPVPQK intervention affected the transcriptomic profiling of the cells. The differentially expressed (DE) genes (FDR < 0.05, and absolute fold change (FC) > 1.5) between VLPVPQK and the model group were mostly enriched in the carbohydrate metabolism-related KEGG pathways. Interestingly, the expression of two core genes (HKDC1 and G6PC1) involved in the above pathways was dramatically elevated after VLPVPQK intervention, which played a key role in regulating glucose metabolism. Furthermore, supplementation of VLPVPQK reversed the high glucose and fat-induced depression of AKR1B10. Overall, VLPVPQK could alleviate the metabolic disorder of hepatocytes by elevating the glucose uptake and eliminating the ROS, while the HKDC1 and AKR1B10 genes might be the potential target genes and play important roles in the process.
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Rare-earth oxide Sm2O3 is theoretically expected to be used in the preparation of ultraviolet (UV) detectors with low dark currents and high radiation resistance due to its characteristics of a wide bandgap, a high dielectric constant, and high chemical stability. However, certain features that rare-earth oxides possess, such as high resistivity and weak photoelectric response currents, have hindered relevant research on these kinds of materials in the field of UV detection. In this work, a p-Gr/i-Sm2O3/n-SiC heterojunction photovoltaic solar-blind UV sensor was constructed for the first time. Because of the high mobility of graphene (Gr) and the contribution of double built-in electric fields in the heterojunction, the collection efficiency of photogenerated carriers has been greatly improved, with the typical shortcomings of high resistivity and poor photoelectric response performance of rare-earth oxides having been overcome. This detector has exhibited outstanding performance at 0 V, including a responsivity of 19.8 mA/W and an open-circuit voltage of 0.68 V. Additionally, this detector has a detectivity as high as 1.2 × 1011 jones, which is at the front position of most ultraviolet detectors. The fabrication of this high-performance Sm2O3-based photovoltaic UV detector has broadened the application fields of rare-earth oxide semiconductors. Therefore, this project has important value for future research in relevant fields.
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Introduction: Natural science education, as an important means to improve the scientific literacy of citizens, combines science education games with virtual reality (VR) technology and is a major developmental direction in the field of gamified learning. Methods: To investigate the impact of VR science education games on learning efficiency from the perspective of embodied cognition, this study uses the China National Knowledge Infrastructure (CNKI) and Web of Science (WOS) databases as the main source of samples. A meta-analysis of 40 studies was conducted to examine teaching content, game interaction, and immersion mode. Results: The study found that (1) VR science and education games have a moderately positive impact on the overall learning effect; (2) regarding teaching content, the learning effect of skill training via VR science and education games is significant; (3) regarding interaction form, the learning effect on active interaction is significantly better than that of passive interaction; (4) regarding immersion mode, somatosensory VR games have a significant impact on the enhancement of students' learning; (5) regarding application disciplines, VR science education games have a greater impact on science, engineering, language and other disciplines; (6) regarding academic segments, the learning effect on college students is most significant; and (7) regarding experimental intervention time, short-term intervention is most effective. Discussion: Accordingly, this article proposes strategies for VR science game design from the perspective of embodied cognition: a five-phase strategy including skill training, human-computer interaction, and environmental immersion, aiming to improve the learning effect and experience of users.
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Background: Left bundle branch pacing (LBBP) is emerging as an effective alternative to achieve cardiac resynchronization therapy (CRT) and improve heart function. The purpose of our study was to investigate the feasibility and efficacy of LBBP in heart failure patients with left ventricular ejection fraction (LVEF) <50% and left bundle branch block (LBBB). Methods: All patients with complete LBBB and LVEF <50% were retrospectively included in the study from April 2018 to April 2021 and underwent CRT via LBBP implantation. ECG, pacing parameters, the New York Heart Association (NYHA) functional class, echocardiographic measurements, and complications were recorded and analyzed at implant and during follow-up of 1, 6, and 12 months. Results: Left bundle branch pacing was successful in all 34 patients (mean age 65.6 ± 11.2 years, 67.6% men). A significant decrease in QRS duration (QRSd) was observed after the LBBP operation for 1 month (153.2 ± 1.7 vs. 111.9 ± 2.6 ms, p < 0.01). LBB capture threshold and R-wave amplitude remained stable at 12-month follow-up when compared with implantation values (0.62 ± 0.13 V @ 0.4 ms vs. 0.73 ± 0.21 V @ 0.4 ms, 12.02 ± 5.68 mV vs. 8.58 ± 4.09 mV, respectively). LVEF increased significantly (35.28 ± 1.70% vs. 51.09 ± 1.71%, p < 0.01) accompanied with reduced left ventricular end-diastolic dimension (LVEDd; 65.3 ± 1.99 vs. 53.58 ± 2.07 mm, p < 0.01) and left atrial dimension (LAD; 49.03 ± 1.32 vs. 40.67 ± 1.58 mm, p < 0.01). Normalized LVEF (LVEF ≥ 50%) was found in 70.5% of patients at 12 months. The NYHA classification, brain natriuretic peptide (BNP), and 6-minute walk test (6MWT) were significantly improved at follow-up of 12 months (all p < 0.01 vs. baseline). No deaths or heart failure hospitalizations were observed during the follow-up period. Conclusion: The current work suggested that LBBP was feasible with a high success implantation rate and effective to correct LBBB and improved left ventricular structure and function with a low and stable pacing threshold.
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BACKGROUND: Cardiac hypertrophy is a compensatory response to pressure overload, which eventually leads to heart failure. The current study explored the protective effect of nicotinamide riboside (NR), a NAD+ booster that may be administered through the diet, on the occurrence of myocardial hypertrophy and revealed details of its underlying mechanism. METHODS: Transverse aortic constriction (TAC) surgery was performed to establish a murine model of myocardial hypertrophy. Mice were randomly divided into four groups: sham, TAC, sham+NR, and TAC+NR. NR treatment was given daily by oral gavage. Cardiac structure and function were assessed using small animal echocardiography. Mitochondrial oxidative stress was evaluated by dihydroethidium (DHE) staining, malondialdehyde (MDA) content, and superoxide dismutase (SOD) activity. Levels of expression of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), IL-1ß, TNF-α, and Sirtuin3 were measured by real-time PCR and ELISA. Expression levels of Caspase-1, Caspase-1 pro, cleaved Gasdermin D (GSDMD), NLRP3, ASC, Sirtuin3, ac-MnSOD, and total MnSOD were measured by Western blot. RESULTS: Reductions in the heart/body mass ratio (HW/BW) and lung/body mass ratio (LW/BW) and in ANP, BNP, and LDH levels were observed in the TAC group on the administration of NR (P < 0.05). Moreover, echocardiography data showed that cardiac dysfunction and structural changes caused by TAC were improved by NR treatment (P < 0.05). NR treatment also reduced levels of the inflammatory cytokines, IL-1ß and TNF-α, and attenuated activation of NLRP3 inflammasomes induced by TAC. Furthermore, changes in DHE staining, MDA content, and SOD activity indicated that NR treatment alleviated the oxidative stress caused by TAC. Data from ELISA and Western blots revealed elevated myocardial NAD+ content and Sirtuin3 activity and decreased acetylation of MnSOD after NR treatment, exposing aspects of the underlying signaling pathway. CONCLUSION: NR treatment alleviated TAC-induced pathological cardiac hypertrophy and dysfunction. Mechanically, these beneficial effects were attributed to the inhibition of NLRP3 inflammasome activation and myocardial inflammatory response by regulating the NAD+-Sirtuin3-MnSOD signaling pathway.