Synthesis of Polymers with Narrow Molecular Mass Distribution through Interface-Initiated Room-Temperature Polymerization in Emulsion Gels.

Homopolymers of n-butyl acrylate, methyl methacrylate, styrene, and their random copolymers were prepared via interface-initiated polymerization of emulsion gels at 20 °C. The polymerization was conducted in a free radical polymerization manner without inert gas protection. Compared with the polymers synthesized at 60 °C, the polymerization of emulsion gels at 20 °C produced homo- and copolymers with a higher molecular mass and a narrower molecular mass distribution. The polydispersity indices for the polymers synthesized at 20 °C were found to be between 1.12 and 1.37. The glass transition temperatures for the as-synthesized butyl acrylate copolymers agree well with the prediction from the Gordon-Taylor equation. Interface-initiated room-temperature polymerization is a robust, energy-saving polymerization technique for synthesizing polymers with a narrow molecular mass distribution.

PARP-1 inhibitor alleviates liver lipid accumulation of atherosclerosis via modulating bile acid metabolism and gut microbes.

Background: The DNA damage repair enzyme, poly(ADP-ribose) polymerase 1 (PARP1), is crucial for lipid and glucose metabolism. However, no evidence has been presented on the relationship between liver lipid accumulation and the PARP1 inhibitor, 3-aminobenzamide (3-AB), in atherosclerosis. Methods: ApoE-/- mice were used to explore the effect of 3-AB on atherosclerotic liver lipid accumulation, and the experiment of Sprague Dawley (SD) rats was designed to determine if the lowering of liver lipid levels by 3-AB was linked to gut bacteria. The levels of bile acid metabolism-related targets were assessed by ELISA, western blotting, and RT-qPCR. The relative abundances of gut microbes and biomarkers were determined using 16S rRNA sequencing analysis. Bile acid levels in the liver and ileum were examined by ultra-performance liquid chromatography-tandem mass spectrometry. The relationship between gut microbes and bile acids was assessed by Spearman's correlation analysis. Results: 3-AB significantly reduced the formation of aortic plaques in apoE-/- mice, according to gross oil red staining. H & E and Oil Red O staining revealed that 3-AB significantly reduced the hepatic lipid droplet area in ApoE-/- mice and SD rats. Compared with the atherosclerosis (ATH) group, 3-AB dramatically decreased the levels of total cholesterol (TC), triglyceride (TG), and low-density lipoprotein-cholesterol (LDL-C) in the serum of SD rats and apoE-/- mice, and the levels of TC, TG, and LDL-C in the serum and liver of apoE-/- mice. Furthermore, in apoE-/- mice and SD rats, 3-AB increased the mRNA and protein levels of farnesoid X receptor (FXR) and bile salt export pump (BSEP) in the liver, while inhibiting the mRNA and protein levels of FXR and fibroblast growth factor 15 (FGF15) in the ileum, respectively. 3-AB clearly inhibited the mRNA and protein levels of PARP1 in the liver and ileum of apoE-/- mice and rats. Following treatment with 3-AB, the levels of conjugated bile acids decreased in the liver of apoE-/- mice and increased in the ileum of SD rats, according to targeted metabolomic analysis. Microbiome sequencing analysis revealed that 3-AB reduced the relative abundance of Lactobacillus, Bifidobacterium, Listeria, Clostridium, Bacillus, and Staphylococcus in the feces of apoE-/- mice, and the relative abundance of Blautia, Clostridium, and Listeria in the feces of SD rats, eventually decreasing the total abundance of 10 bile salt hydrolase-associated gut microbes. According to the correlation analysis, 3-AB regulates bile acid metabolism, which is primarily related to Bifidobacterium. Conclusion: 3-AB alleviated atherosclerosis by modulating the bile acid metabolism and bile salt hydrolase-related gut microbes.

Lamiophlomis rotata attenuates rheumatoid arthritis by regulating sphingolipid and steroid hormone metabolism.

Rheumatoid arthritis (RA) is a chronic and progressive autoimmune disease. Lamiophlomis rotata (L. rotata) (Benth.) Kudo, an essential medicinal plant in traditional Tibetan medicine, is useful in treating RA. The purpose of this study was to evaluate L. rotata's anti-RA effect and to analyze its serum metabolites and lipids to predict the possible action pathways. Female and male rats were immunized with CFA to induce arthritis. Paw volumes were measured, and arthritis index analysis and histological analysis were performed to check the effects of L. rotata. ELISA was used to measure the levels of inflammatory cytokines (IL-1ß, TNF-α, IL-6, and IL-10) and oxidative stress (MDA, SOD, GSH, and CAT). UPLC/Q-Orbitrap-MS was used to identify untargeted metabolites and lipids in serum. Metabolite validation was performed using UPLC/QQQ-MS. L. rotata application significantly reduced arthritis indices and paw swelling in AIA rats, and diminished inflammation and bone fractures in joint tissues. Sphingolipid (SP) and steroid hormone biosynthesis was found to be closely related to L. rotata's intervention in RA. In addition, our experiments also confirmed that females were more likely than males to develop RA. These findings provide clues and a scientific basis for the mechanism of L. rotata in treating RA.

Knowledge, Attitude, Risk Perception, and Health-Related Adaptive Behavior of Primary School Children towards Climate Change: A Cross-Sectional Study in China.

BACKGROUND: Children are disproportionately affected by climate change while evidence regarding their adaptive behavior and relevant influencing factors is limited. OBJECTIVES: We attempted to investigate health-related adaptive behavior towards climate change for primary school children in China and explore potential influencing factors. METHODS: We conducted a survey of 8322 primary school children in 12 cities across China. Knowledge, attitude, risk perception, and adaptive behavior scores for children were collected using a designed questionnaire. Weather exposures of cities were collected from 2014 to 2018. We applied a multiple linear regression and mixed-effect regression to assess the influencing factors of adaptive behavior. We also used the structural equation model (SEM) to validate the theoretical framework of adaptive behavior. RESULTS: Most children (76.1%) were aware of climate change. They mainly get information from television, smartphones, and the Internet. A 1 score increase in knowledge, attitude, and risk perception was associated with 0.210, 0.386, and 0.160 increase in adaptive behavior scores, respectively. Females and children having air conditioners or heating systems at home were positively associated with adaptive behavior. Exposure to cold and rainstorms increased the adaptive behavior scores, while heat exposure had the opposite effects. The SEM showed that knowledge was positively associated with attitude and risk perception. Knowledge, attitude, and risk perception corresponded to 31.6%, 22.8%, and 26.1% changes of adaptive behavior, respectively. CONCLUSION: Most primary school children in China were aware of climate change. Knowledge, attitude, risk perception, cold, and rainstorm exposure were positively associated with health-related adaptive behavior towards climate change.

A nano-preparation approach to enable the delivery of daphnoretin to potentiate the therapeutical efficacy in hepatocellular cancer.

Daphnoretin (DAP), isolated from a traditional Chinese medicine Wikstroemia indica (Linn. C. A. Meyer), could induce apoptosis of hepatocellular cancer (HCC) and inhibit tumor growth. However, the application of DAP in cancer therapies was hampered because to its poor solubility. Herein, this study aimed to design an approach of double-targeted nano-preparation to enable the delivery of DAP to potentiate the therapeutical efficacy in liver cancer via glycyrrhetinic acid-polyethylene glycol-block-poly (D,L-lactic acid)/polyethylene glycol-block-poly (D,L-lactic acid)-DAP (GPP/PP-DAP). In particular, the purity of separated DAP was up to 98.12% for preparation research. GPP/PP-DAP was successfully prepared by the thin-film hydration method. Subsequently, the GPP/PP-DAP was optimized by univariate analysis and the response surface methodology, producing a stable and systemically injectable nano-preparation. Impressively, on the one hand, cytotoxicity studies showed that the IC50 of the GPP/PP-DAP was lower than that of free DAP. On the other hand, the GPP/PP-DAP was more likely to be endocytosed by HepG2 cells and targeted to the liver with orthotopic tumors, potentiating the therapeutical efficacy in HCC. Collectively, both in vitro and in vivo results indicated the excellent tumor inhibition and liver targeting of GPP/PP-DAP, suggesting the nano-preparation could serve as a potential drug delivery system for natural ingredients with anti-hepatoma activity to lay the theoretical foundation for clinical application.

1H-NMR-based metabolic profiling of rat urine to assess the toxicity-attenuating effect of the sweat-soaking method on Radix Wikstroemia indica.

Radix Wikstroemia indica (L.) C.A. Mey. (RWI) is a toxic medicinal species primarily present in the Miao area of China. The toxicity of RWI is effectively reduced whilst maintaining the therapeutic effect when processed using the 'sweat-soaking method', which is a common method of Traditional Chinese Medicine preparation. However, there is a lack of scientific and medical evidence to explain the potential mechanisms by which the toxicity of RWI is reduced after preparation using this method, and the endogenous systemic metabolic effect of RWI remains uncertain. The aim of the present study was to explore the endogetnous metabolic alterations caused by RWI and to examine the possibility of reducing the toxicity of RWI using the sweat-soaking method using proton nuclear magnetic resonance (NMR) metabolomic analysis in rats. Principal Component Analysis, Partial Least Squares-Discriminant Analysis (PLS-DA) and Orthogonal PLS-DA were used to assess individual proton NMR spectra. A total of 34 metabolic products were altered after delivering raw RWI, and 32 endogenous metabolites were induced by processed RWI. The metabolic pathways that lead to a significant impact on energy and carbohydrate, amino acid, organic acids and lipid metabolism following raw and processed RWI use were identified. The mitochondria of hepatic and renal tubules of rats were injured in the raw RWI group, whereas the processed product reduced or interfered with energy substrate, carbohydrate and amino acid metabolism, whilst reducing the levels of metabolic markers of hepatotoxicity and nephrotoxicity, without causing damage to the mitochondria. Our previous study showed that the median lethal dose (LD50) value of raw RWI was 4.05 g/kg in rats after oral administration; however, the LD50 value of the processed RWI could not be measured. The maximum tolerated dose and minimum lethal dose were 20 and 30 g/kg for the processed RWI, respectively, corresponding to 109 and 164 times the clinical daily dose (0.029 g/kg). Thus, the sweat-soaking method reduced the toxicity of RWI. Moreover, after processing, the toxic component YH-10 was converted into a YH-10 + OH compound, reducing the content of the toxic YH-10 by 48%, whilst also reducing the contents of the toxic components YH-12 and YH-15 by 44 and 65%, respectively. In conclusion, the present study showed that the sweat-soaking method reduced the toxicity of RWI, as evidenced by the reduction of the levels of metabolic markers and the activity of metabolic pathways, thus providing a basis for processing of RWI for clinical use.

Impulsivity and craving in subjects with opioid use disorder on methadone maintenance treatment.

BACKGROUND: Methadone maintenance treatment (MMT) is effective in decreasing opioid use or facilitating abstinence. Previous studies using small opioid use disorder samples suggest that cognitive impairments including impulsivity and executive functions may partially improve on MMT, but a range of deficits may persist. However, systematic assessments with larger samples are needed to confirm the profile of cognitive functions on MMT. METHODS: We assessed four types of impulsivity (delay discounting, reflection impulsivity, risk taking and motoric impulsivity), executive functioning (spatial working memory, paired associative learning and strategic planning) and drug cue-induced craving in a relatively large population (115 MMT patients, 115 healthy controls). The relationships between impulsivity, drug cue-induced craving and addiction-related variables were also assessed. RESULTS: Delay discounting, as well as drug cue-induced craving was increased in patients, while motoric impulsivity was lower than in controls. Paired associative learning was additionally impaired, which was explained by increased depression and anxiety levels in patients. Within the MMT group, the delay discounting and drug-cue induced craving scores were positively correlated with self-reported urgency, but unrelated to methadone dosage, duration on methadone, withdrawal symptoms, or presence of nicotine dependence. CONCLUSIONS: Our findings highlight increased delay discounting and cue-induced craving in MMT patients suggesting a potential role for trait effects in delay discounting. Although previous smaller studies have shown impaired executive function, in our large sample size on chronic MMT we only observed impaired associative learning related to depressive and anxiety symptoms highlighting a role for managing comorbid symptoms to further optimize cognitive function.

The Chinese version of obsessive compulsive drug use scale: validation in outpatient methadone maintenance treatment program.

BACKGROUND: The Obsessive Compulsive Drug Use Scale (OCDUS) measures the overall craving level within a period from a multidimensional perspective. However, no studies have addressed the validity of the new OCDUS factor structure, presented in 2016, in China. Additionally, there is lack of evidence on the interaction among risk factors for relapse. We aimed to assess the psychometric properties of the scores of the Chinese version of the OCDUS in patients with heroin dependence receiving methadone maintenance treatment (MMT). Further, we aimed to assess the correlations of the OCDUS scores with withdrawal symptoms, depression, anxiety, and nicotine dependence. METHODS: We enrolled 113 adults (age 32-64 years) and administered them with the OCDUS, Subjective Opioid Withdrawal Scale (SOWS), Beck Depression Inventory-II (BDI-II), State-Trait Anxiety Inventory (STAI), and Fagerstrom Test for Nicotine Dependence (FTND). RESULTS: Exploratory factor analysis identified a 3-dimensional component that included "Frequency of craving," "Inference of heroin," and "Control of heroin." These factors showed acceptable internal consistency, adequate item-total correlations, and significant item-subscale correlations. There was no correlation between the OCUDS scores and age, education, duration of receiving MMT, and MMT dosages. However, there was a significant correlation between the OCDUS total scores and the SOWS, STAI, BDI-II, and FTND scores. The scores of all the subscales were associated with the SOWS scores; further, the scores of the first two subscales were associated with BDI-II scores while only the scores of the first subscale were associated with the FTND scores. CONCLUSIONS: Our findings support the reliability and structure validity of the OCDUS scores. Heroin craving, withdrawal symptoms, negative emotions, and nicotine dependence, which are considered as risk factors for heroin relapse, might interact with each other. There is a need for further studies on the underlying mechanism of these clinical phenomena.

Psychometric Properties of the Chinese version of UPPS-P Impulsive Behavior Scale.

OBJECTIVE: The present study aimed to assess the psychometric properties of a Chinese version of the UPPS-P Impulsive Behavior Scale. The associations between the UPPS-P scale and impulsivity choice, gender, smoking, and drinking status were also assessed. METHODS: A total of 127 adults ranging from 21 to 65 years old participated in the study. Participants were administered with the Chinese version of the UPPS-P Impulsive Behavior Scale, Beck Depression Inventory II (BDI-II), and State-Trait Anxiety Inventory (STAI). Impulsivity choice tasks were also tested including the Delay Discounting Task (DDT), Balloon Analogue Risk Task (BART), and Beads Task (Beads). RESULTS: A new version of the UPPS-P Impulsive Behavior Scale was formed that includes 40 items. The scores of the UPPS-P Impulsive Behavior Scale demonstrated adequate internal consistency on five subscales but less sufficient structure validity in the present sample. In addition, positive urgency was negatively related to the Beads task; negative urgency and positive urgency were positively related to the DDT and BART. Moreover, positive and negative urgency were positively correlated with depression; all five subscales were positively correlated with anxiety; sensation seeking was higher in males than females and in alcohol drinkers than non-drinkers; and lack of premeditation and lack of perseverance were higher in nonsmokers than smokers. CONCLUSIONS: The present study supports the reliability but not the structure validity of the UPPS-P Impulsive Behavior Scale. The impulsivity personality trait assessed by the UPPS-P scale was associated with impulsivity choice, depression, anxiety, gender, and drinking and smoking status. Further studies should be conducted to explore the structure of impulsivity in the Chinese population.

Thermodynamics Analysis of Multiple Microelements' Coupling Behavior in High Fatigue Resistance 50CrVA Spring Steel with Nanoparticles.

Solid solution and coupling precipitation behavior of multiple microelements in 50CrVA spring steel under different temperatures were analyzed based on thermodynamics. Quantitative relationships between the multiple microelements' contents and secondary phases, and their effects on fatigue life, were systematically studied in conjunction with the secondary phase microstructure characterization using scanning and transmission electron microscopy, etc. The solid solution contents of different microelements decreased as the temperature decreased, especially N and Ti, but the number of compounds gradually increased when the temperature decreased. Carbonitride constitutional liquation occurred in 50CrVA-S1# spring steel-containing microparticles, and without carbonitrides, constitutional liquation occurred in 50CrVA-S2# spring steel-containing nanoparticles. The experimental results indicate that the fatigue life reduces by about an order of magnitude when the secondary phase size changes from nanometers to microns, and the corresponding relationship among multiple microelements, microstructure of secondary phases, and fatigue life, was established in this spring steel.