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Radix Scrophulariae (Chinese name: Xuanshen), a traditional Chinese herb, is used for the treatment of hyperthyroidism, and in this study, its mechanisms were evaluated by metabonomics and system pharmacology. To study the anti-hyperthyroidism effects of R. Scrophulariae , a male SD rat (180–220 g) model of hyperthyroidism induced by Euthyrox was used. Thirty rats were randomly distributed into three groups: the Model group, the R. Scrophulariae treatment group (RS group) and the healthy Control group. Using the UHPLC/Q-TOF-MS metabolomics approach, 44 metabolites were found to be profoundly altered in the model group, and the levels of these biomarkers were significantly decreased after treatment with R. Scrophulariae. Forty-four metabolites and 13 signaling pathways related to R. Scrophulariae , including the biosynthesis of unsaturated fatty acids, primary bile acid biosynthesis and sphingolipid metabolism, were explored, and linoleic acid metabolism and sphingolipid metabolism were identified as the most relevant metabolic pathways. In addition, the system pharmacology paradigm revealed that R. Scrophulariae contains 83 active ingredients and is related to 795 genes, and 804 disease genes are related to hyperthyroidism. The construction of the R. Scrophulariaceae -chemical composition-target-hyperthyroidism network identified a total of 112 intersection genes. The enriched gene targets were analyzed, and five pathways were found to be enriched. Among them pathways, the HIF signaling pathway had the highest enrichment score, which indicated that this pathway might be the main signaling pathway related to the treatment of hyperthyroidism by R. Scrophulariae.The integrated approach involving metabolomics and network pharmacology revealed that R. Scrophulariae might play a role in the treatment of hyperthyroidism by regulating the "IL6-APOA1-cholesterol" pathway and disturbing the HIF signaling pathway. The results demonstrate that the combination of metabolomics and network pharmacology could be used to reflect the effects of R. Scrophulariae on the biological network and metabolic state of hyperthyroidism and to evaluate the drug efficacy of R. Scrophulariaceae and its related mechanisms. [ABSTRACT FROM AUTHOR]

Objective To investigate the effect and possible mechanism of extracts of Xuanshen (Scrophularia Root, Radix Scrophulariae) on liver metabolome in rat model of hyperthyroidism. Methods The rat liver metabolites spectrums effected by Euthyrox and Xuanshen extracts were analyzed by using ultra high performance liquid chromatography-time off light-mass spectrometry (UPLCTOFMS). The difference in metabolites spectrums was studied between blank group and model group by using orthogonal partial least squares-discriminant analysis (OPLS DA). The potential biomarkers were found in liver through variable importance projection (VIP). The interventional effects of Xuanshen extracts were discussed through comparing the difference in content of potential biomarkers. Results There were 21 potential biomarkers found in rat liver in model group, and among them 14 metabolites were significantly called back by Xuanshen extracts. The biosynthesis of glycosylphosphatidylinositol (GPI)-anchor, and metabolisms of arachidonic acid, purine, α-linolenic acid, linoleic acid, glutathione and glycerophospholipid were significantly improved by Xuanshen extracts in Euthyrox induced hyperthyroidism rat model. Conclusion Xuanshen extracts can play a role of treating hyperthyroidism through improving relevant liver potential biomarkers and metabolism pathways in hyperthyroidism rat model. [ABSTRACT FROM AUTHOR]

To solve the problem that the natural frequency of deck arch bridges would decrease rapidly when the span increases, a novel arch bridge structure named deck V-arch bridge is proposed. The V-shaped members are added between the main girders and the arch ribs to increase the stiffness of the arch bridge, thereby increasing the natural frequency of the structure. Through the timely conversion of the structural system, the first-phase dead load is carried by the arch ribs, while the second-phase dead load and live load are carried by the variable height truss with main girders as upper chords, arch ribs as lower chords, and V-shaped members as webs, with multi-point elastic constraints. The entire structure has the advantages of arch and truss. In order to verify the correctness of the research and calculation of the dynamic characteristics of the deck V-arch bridge, a test bridge with a span of 10 m is built. The first natural frequency of the vertical bending in the plane of the bridge is tested by utilzing the pulsation test. The stiffness and dynamic characteristics are calculated by utilizing the finite element software. The influence of V-shaped member stiffness on the natural frequency and that of the number of V-shaped members on the temperature stress of the structure are analyzed. The necessity of system transformation is studied. The results show that the difference between test value and calculated value of the first natural frequency of vertical bending in the plane is small. The mode shape is in good agreement with the finite element analysis. With little or no additional material, the natural frequency of the structure is significantly increased, especially the in-plane frequency. The stiffness of the V-shaped members has a reasonable setting range. When the inner angles of the triangle formed by the main girders or the arch ribs are between 45 ℃ and 60 ℃,the number of V-shaped web members is suitable. The structural stiffness of deck arch bridge with V-shaped members is greatly improved, and at the position of L/4 (L is the span of the bridge), the upward deflection generated by the static live load of the train is approximately zero. After the transformation of the structural system, the deck V-arch bridge can fully exert the superiority of the arch force.

Background: Osteoarthritis (OA) is the most common degenerative joint disease worldwide. Further improving the current limited understanding of osteoarthritis has positive clinical value., Methods: OA samples were collected from GEO database and endoplasmic reticulum related genes (ERRGs) were identified. The WGCNA network was further built to identify the crucial gene module. Based on the expression profiles of characteristic ERRGs, LASSO algorithm was used to select key factors according to the minimum λ value. Random forest (RF) algorithm was used to calculate the importance of ERRGs. Subsequently, overlapping genes based on LASSO and RF algorithms were identified as ERRGs-related diagnostic biomarkers. In addition, OA specimens were also collected and performed qRT-PCR quantitative analysis of selected ERRGs., Results: We identified four ERRGs associated with OA risk assessment through machine learning methods, and verified the abnormal expressions of these screened markers in OA patients through in vitro experiments. The influence of selected markers on OA immune infiltration was also evaluated., Conclusions: Our results provide new evidence for the role of ER stress in the OA progression, as well as new markers and potential intervention targets for OA.

Hepatocellular Carcinoma (HCC) is the predominant cause of cancer-related mortality worldwide. The majority of HCC patients are diagnosed at advanced stages of the disease, with a high likelihood of metastasis and unfavorable prognosis. Anoikis resistance is a crucial factor contributing to tumor invasion and metastasis, although its specific role in HCC remains unclear. Based on the results of univariate Cox regression and least absolute shrink-age and selection operator (LASSO) analysis, a subset of anoikis-related genes (ARGs) significantly associated with overall survival (OS) was identified. A multivariate Cox regression analysis subsequently identified PDK4, STK11, and TFDP1 as three prognostic ARGs, which were then used to establish a prognostic risk model. Differences in OS caused by risk stratification in HCC patients were demonstrated. The nomogram analysis indicated that the ARGs prognostic signature served as an independent prognostic predictor. In vitro experiments further confirmed the abnormal expression of selected ARGs in HCC. The association between risk scores and OS was further examined through Kaplan-Meier analysis, CIBERSORT analysis, and single-sample gene set enrichment analysis (ssGSEA). This study is a pioneering effort to integrate multiple ARGs and establish a risk-predictive model, providing a unique perspective for the development of personalized and precise therapeutic strategies for HCC.

Extreme weather can cause ill health in older persons due to a direct thermal effect on the body's thermoregulation and difficulties in maintaining a healthy lifestyle and accessing the health services they need. To understand experiences in relation to their exposures to extreme weather and how they responded to such weather conditions, including cold snaps, heat and air pollution in northern Thai communities, a descriptive qualitative study was conducted to uncover details and the essence of perspectives and experiences of older persons and family members. Three focus group discussions with 15 older persons and 15 family members occurred in three communities in Chiang Rai, a northern province of Thailand. Thematic analysis was performed. Experiences of older persons and families in relation to extreme weather conditions were described in five themes: local actions against weather changes, the double challenges, awareness and reactions to weather changes, protective and comfortable living environments, and mitigation of the impacts of weather conditions. Seasonal adaptability was key for older persons to stay safe and healthy during extreme weather changes. Heat, cold snaps, and air pollution made health and daily living routine maintenance among older persons challenging, especially among those with declining health. Older persons and families employed predictive and adaptive strategies to avoid and minimise extreme weather impacts and maximise their comfort and optimal living.