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[Abstract]: [Objective]: To analyze the main syndrome types, medication rules, and core prescription characteristics of traditional Chinese medicine (TCM) in the treatment of metabolism-associated fatty liver disease (MAFLD), and to predict the anti-MAFLD mechanism of core formula, so as to provide references for the clinical application of TCM and the development of new drugs. [Methods]: Literature research on TCM in treating MAFLD was retrieved from China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), and Wanfang Database since the establishment of the database to July 2022. Excel 2019 and Chinese Medicine Inheritance Computing Platform (V3.0) were used for frequency analysis, association rule analysis, and cluster analysis of effective prescriptions. The key components, targets, and action pathways of anti-MAFLD core formulas were predicted by network pharmacology. Finally, the interactions between the obtained core components and their core targets were verified reversely by molecular docking technology. [Results]: A total of 218 articles were screened and selected, including 352 prescriptions, involving 270 traditional Chinese herbs. The drugs were used a total of 3 901 times, and a total of 10 915 cases were collected, among which the prevalence rate was higher in males. The main types of TCM syndrome included intermingled phlegm and blood stasis syndrome, liver depression and spleen deficiency syndrome, and damp-heat in liver and gallbladder syndrome, among which Shanzha (Crataegi Fructus), Danshen (Salviae Miltiorrhizae Radix et Rhizoma), Fuling (Poria), Zexie (Alismatis Rhizoma), Chaihu (Bupleuri Radix), and Baizhu (Atractylodis Macrocephalae Rhizoma) were the most frequently used. The properties of Chinese medicine primarily encompassed thermal characteristics, with a predominant emphasis on cold and warm; the flavors of herbs were predominantly characterized by bitterness and sweetness, while the majority exhibited tropism towards the spleen and liver meridians. The drugs were primarily classified based on their efficacy in tonifying deficiencies, promoting diuresis and moistening, enhancing blood circulation and removing blood stasis, heat-clearing, etc. The association rules were employed to derive a set of 20 core drug pairs, while cluster analysis was utilized to identify three distinct groups of core drug combinations. Network pharmacological showed that the main components of the core formula “Shanzha (Crataegi Fructus) - Danshen (Salviae Miltiorrhizae Radix et Rhizoma) - Zexie (Alismatis Rhizoma) - Chaihu (Bupleuri Radix) - Fuling (Poria)” in the treatment of MAFLD were quercetin, apigenin, puerarin, luteolin, ursolic acid, kaempferol, tanshinone IIA, emodin, paeonol, etc., which involved RAC-alpha serine/threonine-protein kinase 1 (AKT1), cellular tumor antigen p53 (TP53), interleukin (IL)-6, IL-1β, signal transducer and activator of transcription 3 (STAT3), epidermal growth factor receptor (EGFR), peroxisome proliferative activated receptor gamma (PPARG), and other key targets. The molecular docking results showed that the core components had good binding to lipid and atherosclerosis, and phosphatidylinositol 3 kinase (PI3K)/AKT signaling pathway-associated proteins. [Conclusion]: The main principles of TCM for the treatment of MAFLD involve soothing the liver and strengthening the spleen, eliminating phlegm and dampness, clearing heat and dampness, as well as promoting blood circulation and removing blood stasis. The core formula may exert anti-MAFLD effects mediated through multiple components, targets, and signaling pathways. This study establishes a theoretical foundation for the clinical application of TCM in the treatment of MAFLD, and serves as a reference for further exploration of new drugs against MAFLD.

The presence of interstitial electrons in electrides endows them with interesting attributes, such as low work function, high carrier concentration, and unique magnetic properties. Thorough knowledge and understanding of electrides are thus of both scientific and technological significance. Here, we employ first-principles calculations to investigate Mott-insulating Ae5X3 (Ae = Ca, Sr, and Ba; X = As and Sb) electrides with Mn5Si3-type structure, in which half-filled interstitial electrons serve as ions and are spin-polarized. The Mott-insulating property is induced by strong electron correlation between the nearest interstitial electrons, resulting in spin splitting and a separation between occupied and unoccupied states. The half-filled antiferromagnetic configuration and localization of the interstitial electrons are critical for the Mott-insulating properties of these materials. Compared with that in intermetallic electrides, the orbital hybridization between the half-filled interstitial electrons and the surrounding atoms is weak, leading to highly localized magnetic centers and pronounced correlation effects. Therefore, the Mott-insulating electrides Ae5X3 have very large indirect bandgaps (∼0.30 eV). In addition, high pressure is found to strengthen the strong correlation effects and enlarge the bandgap. The present results provide a deeper understanding of the formation mechanism of Mott-insulating electrides and provide guidance for the search for new strongly correlated electrides. [ABSTRACT FROM AUTHOR]

Loop subdivision is a significant surface scheme with wide applications in fields like computer graphics and wavelet. As a type of stationary scheme, Loop subdivision cannot adjust the limit surface directly. In this paper, we present a new way to solve this problem by proposing a symmetric non-stationary Loop subdivision based on a suitable iteration. This new scheme can be used to adjust the limit surfaces freely and thus can generate surfaces with different shapes. For this new scheme, we show that it is C 2 convergent in the regular part of mesh and is at least tangent plane continuous at the limit positions of the extraordinary points. Additionally, we present a non-uniform generalization of this new symmetric non-stationary subdivision so as to locally control the shape of the limit surfaces. More interestingly, we present the limit positions of the initial points, both for the symmetric non-stationary Loop subdivision and its non-uniform generalization. Such limit positions can be used to interpolate the initial points with different valences, generalizing the existing result. Several numerical examples are given to illustrate the performance of the new schemes. [ABSTRACT FROM AUTHOR]

The purposes of this study were to explore whether the Toll-like receptor 4 (TLR4) gene rs7873784 G/C polymorphism was related to the risk of rheumatoid arthritis (RA) and to the clinical features of the disease in Chinese subjects. We examined the TLR4 rs7873784 G/C polymorphism in 805 Chinese RA patients and 1095 healthy controls. Genotype was determined with a custom-by-design 48-Plex single nucleotide polymorphism scan™ Kit. Blood plasma levels of TLR4 in 170 RA patients and 170 matched controls were measured by ELISA. The TLR4 gene rs7873784 G/C polymorphism was related to a reduced risk for RA. By stratified analysis, we found a dramatically reduced risk for RA in patients who were female, CRP-positive, RF-positive, DAS28 ≥ 3.20, or ESR ≥ 25. Compared with the controls, the average level of TLR4 protein in plasma of RA patients was increased. In addition, RA patients exhibited higher levels of TLR4 mRNA than controls (P <.05). These results demonstrate the TLR4 rs7873784 G/C polymorphism to relate to a decreased risk for RA in a Chinese population. [ABSTRACT FROM AUTHOR]

Interleukin-1 receptor-associated kinase-3 (IRAK3) has a distinctive role in regulating inflammation. However, the functional role of IRAK3 and regulatory mechanism underlying the pathogenesis of osteoarthritis (OA) remain unclear. Here, we first found that IRAK3 was upregulated, while miR-33b-3p was downregulated in the cartilage of OA patients and IL-1β-induced CHON-001 cells. IRAK3 was confirmed as the direct target of miR-33b-3p and negatively regulated by miR-33b-3p. There was an inverse correlation between IRAK3 mRNA expression and miR-33b-3p expression in OA cartilage tissues. The in vitro functional experiments showed that miR-33b-3p overexpression caused a remarkable increase in viability, a significant decrease in inflammatory mediators (IL-1β and TNF-α), and apoptosis in IL-1β-induced CHON-001 cells. Importantly, IRAK3 knockdown imitated, while overexpression reversed the effects of miR-33b-3p on IL-1β-induced inflammation and apoptosis in CHON-001 cells. Collectively, miR-33b-3p significantly alleviated IL-1β-induced inflammation and apoptosis by downregulating IRAK3, which may serve as a promising target for OA. [ABSTRACT FROM AUTHOR]