Proteome-wide Mendelian randomization identifies potential therapeutic targets for nonalcoholic fatty liver diseases.

Nonalcoholic fatty liver disease (NAFLD) is the predominant cause of liver pathology. Current evidence highlights plasma proteins as potential therapeutic targets. However, their mechanistic roles in NAFLD remain unclear. This study investigated the involvement of specific plasma proteins and intermediate risk factors in NAFLD progression. Two-sample Mendelian randomization (MR) analysis was conducted to examine the association between plasma proteins and NAFLD. Colocalization analysis determined the shared causal variants between the identified proteins and NAFLD. The MR analysis was applied separately to proteins, risk factors, and NAFLD. Mediator shares were computed by detecting the correlations among these elements. Phenome-wide association studies (phewas) were utilized to assess the safety implications of targeting these proteins. Among 1,834 cis-protein quantitative trait loci (cis-pQTLs), after-FDR correction revealed correlations between the plasma levels of four gene-predicted proteins (CSPG3, CILP2, Apo-E, and GCKR) and NAFLD. Colocalization analysis indicated shared causal variants for CSPG3 and GCKR in NAFLD (posterior probability > 0.8). Out of the 22 risk factors screened for MR analysis, only 8 showed associations with NAFLD (p ≤ 0.05), while 4 linked to CSPG3 and GCKR. The mediator shares for these associations were calculated separately. Additionally, reverse MR analysis was performed on the pQTLs, risk factors, and NAFLD, which exhibited a causal relationship with forward MR analysis. Finally, phewas summarized the potential side effects of associated-targeting proteins, including CSPG3 and GCKR. Our research emphasized the potential therapeutic targets for NAFLD and provided modifiable risk factors for preventing NAFLD.

Microstructural Evolution of P(NDI2OD-T2) Films with Different Molecular Weight during Stretching Deformation.

Conjugated polymers exhibit excellent electrical and mechanical properties when their molecular weight (Mw) is above the critical molecular weight (Mc). The microstructural changes of polymers under strain are crucial to establish a structure-performance relationship. Herein, the tensile deformation of P(NDI2OD-T2) is visualized, and cracks are revealed either along the (100) crystal plane of side chain packing or along the main chain direction which depends on the Mw is below or above the Mc. When Mw < Mc, the film cracks along the (100) plane under small strains. When Mw > Mc, the polymer chains first undergo stretch-induced orientation and then fracture along the main chain direction at large strains. This is attributed to the fact that the low Mw film exhibits large crystalline domains and the absence of interdomain connectivity, which are vulnerable to mechanical stress. In contrast, the high Mw film displays a nearly amorphous morphology with adequate entanglements, the molecular chains can endure stresses in the stretching direction to release substantial strain energy under greater mechanical deformation. Therefore, the film with Mw > Mc exhibits the optimal electrical and mechanical performances simultaneously, i.e., the electron mobility is retained under 100% strain and after 100 stretching-releasing cycles.

Spillover Effect of the Internet on Trade Performance Based on a Vision of the Public's Sleep Health: A Spatial Study of the Global Network.

This is the first study to analyze the spatial spillover effect of the internet on trade performance based on a vision of the public's sleep health. The internet's effect on trade performance has been enhanced in a new economy consisting of larger global markets. An overall improvement in health gradually impacts economic development. In this study, hierarchical modeling is applied to reveal the effect of the internet on trade performance at a fundamental level, and the effect of sleep health on trade performance at general level. The global network is structured by a spatial weight matrix based on the Mahalanobis distance of the internet and sleep health. Furthermore, spatial autoregressive modeling is applied to study the effect of the spatial weight matrix based on the Mahalanobis distance matrix of the internet and sleep health on trade performance. The spatial Durbin modeling is applied to further analyze the interaction effect of the spatial weight matrix and countries' factors on trade performance. It was found that the internet has a positive effect on trade performance, and good sleep health can be helpful to the spillover effect of the internet on trade performance. The interaction of the spatial weight matrix and gross domestic product (GDP) can further enhance the effect. This research can assist global managers to further understand the spatial spillover effect of the internet on trade performance based on a vision of the public's sleep health.

[Researches on pyretic pulmonary syndrome model interfered by Scutellariae Radix based on variation of biomarker].

OBJECTIVE: Metabonomics researches of Scutellariae Radix interfering pyretic pulmonary syndrome had been done, to determine the specific biomarkers of pyretic pulmonary syndrome, and to approach the mechanism that Scutellariae Radix interfered the variation of these biomarkers. METHOD: Metabonomics technique, UPLC-Q-TOF/MS analytical means and PCA statistical methods were utilized to investigate the trajectory change and inter-relationship of urinary metabolome of rats treated differently. RESULT: Six specific biomarkers were determined which could represent Streptococcus pneumoniae-induced pyretic pulmonary syndrome in rats. Scutellariae Radix could significantly adjust the ascended biomarkers to the normal level. Meanwhile two of these biomarkers were identified as Delta-12-prostaglandin J2 and indoxyl sulfate. CONCLUSION: There was a good therapeutic function of Scutellariae Radix on pyretic pulmonary syndrome, which was elucidated on the metabolic aspects. There was also a correlationship between the mechanism of Scutellariae Radix curing pyretic pulmonary syndrome and the six specific biomarkers.

[Effects of Chinese herbal medicine Huanglian Jiedu Decoction on urine metabonomics of healthy people].

OBJECTIVE: To study biomarkers and their diversification in healthy people's urine before and after oral administration of Huanglian Jiedu Decoction, a compound Chinese herbal medicine, and to investigate the influence of Huanglian Jiedu Decoction on urine metabonomics of healthy people. METHODS: Ten healthy volunteers joined in this experiment and signed informed consent. They were given oral administration of Huanglian Jiedu Decoction for 3 days, and their urine was collected every morning. The samples were centrifuged at 13 000×g for 10 min at 4 degrees centigrade, and the supernatant was stored at -75 degrees centigrade. The samples were examined by a core technology called ultra-performance liquid chromatography quadruple time of flight/mass spectrometry and then the data were analyzed by principal components analysis and partial least square-discriminant analysis to investigate trajectory diversification and corresponding relations of the time and amount of urine metabonomics before and after oral administration of Huanglian Jiedu Decoction. RESULTS: Evident variance of urine metabonomics took place after oral administration of Huanglian Jiedu Decoction, which showed that the metabolism of healthy people had been visibly affected. Seven potential biomarkers which play a role in healthy people on behalf of Huanglian Jiedu Decoction were preliminarily found, and one biomarker which had biological significance was identified as 2-(formylamino)-benzoic acid. CONCLUSION: The effects of Huanglian Jiedu Decoction on urine metabonomics in healthy people investigated at the level of metabolism can provide theoretical and technical support for the study of Huanglian Jiedu Decoction's influence on heat syndrome.