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MicroRNAs (miRNAs) are endogenous noncoding RNAs that mediate the fibrotic process by regulating multiple targets. MicroRNA-based therapy can restore or inhibit miRNA expression and is expected to become an effective approach to prevent and alleviate fibrotic diseases. However, the safe, targeted, and effective delivery of miRNAs is a major challenge in translating miRNA therapy from bench to bedside. In this review, we briefly describe the pathophysiological process of fibrosis and the mechanism by which miRNAs regulate the progression of fibrosis. Additionally, we summarize the miRNA nanodelivery tools for fibrotic diseases, including chemical modifications and polymer-based, lipid-based, and exosome-based delivery systems. Further clarification of the role of miRNAs in fibrosis and the development of a novel nanodelivery system may facilitate the prevention and alleviation of fibrotic diseases in the future. [ABSTRACT FROM AUTHOR]

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Most cancer causal variants are found in gene regulatory elements, e.g., enhancers. However, enhancer variants predisposing to hepatocellular carcinoma (HCC) remain unreported. Here we conduct a genome-wide survey of HCC-susceptible enhancer variants through a three-stage association study in 11,958 individuals and identify rs73613962 (T > G) within the intronic region of PRMT7 at 16q22.1 as a susceptibility locus of HCC (OR = 1.41, P = 6.02 × 10−10). An enhancer dual-luciferase assay indicates that the rs73613962-harboring region has allele-specific enhancer activity. CRISPR-Cas9/dCas9 experiments further support the enhancer activity of this region to regulate PRMT7 expression. Mechanistically, transcription factor HNF4A binds to this enhancer region, with preference to the risk allele G, to promote PRMT7 expression. PRMT7 upregulation contributes to in vitro, in vivo, and clinical HCC-associated phenotypes, possibly by affecting the p53 signaling pathway. This concept of HCC pathogenesis may open a promising window for HCC prevention/treatment. The role of enhancer variants in hepatocellular carcinoma (HCC) predisposition remains unknown. Here, the authors perform a genome-wide survey of HCC-susceptible enhancer variants in 11,958 individuals, identify rs73613962 within the intronic region of PRMT7 and find that PRMT7 upregulation predisposes to HCC. [ABSTRACT FROM AUTHOR]

Background: The 2019 novel coronavirus disease (COVID-19) has had a massive impact on public health, resulting in sudden dietary and behavioral habit changes. Frontline epidemic prevention workers play a pivotal role against COVID-19. They must face high-risk infection conditions, insufficient anti-epidemic material supplies, mental pressure, and so on. COVID-19 seriously affects their dietary and behavioral habits, and poor habits make them more susceptible to COVID-19. However, their baseline dietary and behavioral habits before COVID-19 and their willingness to change these habits after the outbreak of COVID-19 remain unclear for these workers in China. This study aimed to explore the baseline dietary and behavioral habits of frontline workers and their willingness to change these habits after the outbreak of the epidemic; in addition, susceptible subgroups were identified by stratified analyses as targets of protective measures to keep them from being infected with COVID-19. Methods: A cross-sectional study was conducted through an online questionnaire using a sample of 22,459 valid individuals living in China, including 9402 frontline epidemic prevention workers. Results: Before COVID-19, 23.9% of the frontline epidemic prevention workers reported a high-salt diet, 46.9% of them reported a high frequency of fried foods intake, and 50.9% of them smoked cigarettes. After the outbreak of COVID-19, 34.6% of them expressed a willingness to reduce salt intake, and 43.7% of them wanted to reduce the frequency of pickled vegetables intake. A total of 37.9% of them expressed a willingness to decrease or quit smoking, and 44.5% of them wanted to increase sleep duration. Significant differences in the baseline dietary and behavioral habits and the willingness to change their habits were observed between frontline epidemic prevention workers and other participants. Among the frontline epidemic prevention workers with poor dietary and behavioral habits before COVID-19, frontline epidemic prevention experience was a promoting factor for adopting worse dietary and behavioral habits, including those in the high-salt intake subgroup (OR, 2.824; 95% CI, 2.341–3.405) and the 11–20 cigarettes/day subgroup (OR, 2.067; 95% CI, 1.359–3.143). Conclusions: The dietary and behavioral habits of frontline epidemic prevention workers were worse than that those of other participants before COVID-19. They had a greater willingness to adopt healthy dietary and behavioral habits after experiencing the outbreak of COVID-19. However, frontline epidemic prevention workers with poor dietary and behavioral habits before COVID-19 continued in engage in these poor habits. Dietary and behavioral intervention policies should be drafted to protect their health, especially frontline epidemic prevention workers with poor habits at baseline. [ABSTRACT FROM AUTHOR]

The current investigation is trying to study the impact of the mixture of Chinese herbs Qi Wei Bai Zhu San (QWBZS) on bacterial lactase gene from antibiotics-induced diarrhea (AAD) mice, as the good curative effect of QWBZS on diarrhea. Mice (6 mice per group) were randomly selected as control, model and treatment groups. To induce diarrhea, mice in both model and treatment groups were intragastrically injected with mixture of gentamycin sulfate and cefradine (23.33 mL kg day) twice per day and continuously for totally 5 days. After the success of establishing diarrhea model, the mice in treatment group were gavaged with QWBZS for 3 days. Intestinal contents in all three groups were then collected and DNA was extracted in aseptic environment for the following sequencing. The results showed that mice from QWBZS treatment group had obviously detectable levels of intestinal bacteria, such as Actinobacteria, Firmicutes and Proteobacteria, which produce phyla lactase specifically. In comparison with other groups, the mice in treatment group had more abundant expression of lactase gene from Acidovorax sp. KKs102, Stenotrophomonas sp. LMG11000, Pseudomonas oleovorans, Eggerthella and Burkholderia. Interestingly, the Shannon index decreased significantly after the treatment with QWBZS ( P < 0.01 or P < 0.05). 63.1% of lactase genes detected in the mice in treatment group were unclassified, and 32.8% of them were non-homologous to any fragments in the gene bank, which means that most of lactase-producing bacteria are novel. Our results indicate that treatment with QWBZS did not increase the diversity of bacterial lactase gene. Its curative effect on diarrhea may be relevant to its role in facilitating the growth of novel or some key lactase-producing strains. [ABSTRACT FROM AUTHOR]

We used the Rule Space Model, a cognitive diagnostic model, to measure the learning progression for thermochemistry for senior high school students. We extracted five attributes and proposed their hierarchical relationships to model the construct of thermochemistry at four levels using a hypothesized learning progression. For this study, we developed 24 test items addressing the attributes of exothermic and endothermic reactions, chemical bonds and heat quantity change, reaction heat and enthalpy, thermochemical equations, and Hess's law. The test was administered to a sample base of 694 senior high school students taught in 3 schools across 2 cities. Results based on the Rule Space Model analysis indicated that (1) the test items developed by the Rule Space Model were of high psychometric quality for good analysis of difficulties, discriminations, reliabilities, and validities; (2) the Rule Space Model analysis classified the students into seven different attribute mastery patterns; and (3) the initial hypothesized learning progression was modified by the attribute mastery patterns and the learning paths to be more precise and detailed. [ABSTRACT FROM AUTHOR]

To investigate the influence of Debaryomyces hansenii treatment on intestinal microorganisms in mice with antibiotics-induced diarrhea, mouse model of antibiotics-induced diarrhea was created by gavaging mice with mixed antibiotics (23.33 mL/kg/days) composed of gentamycin sulfate and cefradine for 5 days. Mice with the symptom of diarrhea were then treated with D. hansenii by intragastric administration. The control group mice were given with sterile water. After 4 day treatment, total DNA of intestinal microflora of treated and control mice was extracted, and their quantities were measured by sequencing the V4 region of 16S rDNA. The results showed that when compared to the control (sterile water), treatment with D. hansenii increased the operational taxonomic units (OTUs) of intestinal bacteria. The Chao index in diarrhea treated group was higher than diarrhea control group and was similar to healthy control group, while all differences had no significance ( P > 0.05). D. hansenii treatment increased the Shannon index but not significantly ( P > 0.05). Moreover, there was not significant impact on density and diversity of intestinal bacterial population at phylum and genus levels ( P > 0.05). Interestingly, D. hansenii treatment recovered the population density of certain bacterium species, such as Bacteroidaceae (in family level) ( P < 0.05). Our results indicate that D. hansenii has potency of adjusting the density and diversity of intestinal bacteria and recovering the population density of Bacteroidaceae in family level. [ABSTRACT FROM AUTHOR]

Fraction 18 (100%) was chromatographed on silica gel (petroleum ether-EtOAc, 10:1) followed by recrystallization and Sephadex LH-20 chromatography (methanol 100%) to give compounds B 8 b (24.9 mg) and B 9 b (4.9mg). A portion of the petroleum ether fraction (221.84 g) was subjected to silica gel column chromatography by a gradient-elution technique with a mobile phase of petroleum ether-EtOAc (1:0-1:1), and nine fractions (F1-F9) were obtained according to TLC results. All the nine compounds were isolated and identified for the first time from the fruiting bodies of I O. raphanipes. i Furthermore, the anticancer activity of the petroleum ether extract I in vitro i was studied by employing the CCK8 (cell counting Kit-8) assay method [[13]] (Table 1). [Extracted from the article]

Objective: To explore inadequate and excessive gestational weight gain (GWG) among pregnant women of different racial/ethnic backgrounds in Ontario, Canada., Methods: A population-based retrospective cohort study was conducted among women who had prenatal screening and had a singleton birth in an Ontario hospital between April 2016 and March 2017. We estimated adjusted risk ratios (aRR) of racial/ethnic differences for inadequate or excessive GWG using multinomial logistic regression models. Interaction effects were examined to determine whether racial/ethnic difference in GWG varied by pre-pregnancy body mass index (BMI)., Results: Among 74,424 women, the prevalence of inadequate GWG in White, Asian, and Black women was 15.7%, 25.8%, and 25.0%, and excessive GWG was 62.8%, 45.5%, and 54.7%, respectively. There were significant interaction effects between race/ethnicity and pre-pregnancy BMI for inadequate GWG (Wald p < 0.01) and excessive GWG (Wald p < 0.01). Compared with White women, Asian women had higher risk of inadequate GWG and lower risk of excessive GWG in all weight classes, and Black women had higher risk of inadequate GWG and lower risk of excessive GWG if their BMI was normal, overweight, or obese., Conclusion: Variations in unhealthy GWG by pre-pregnancy weight classes among Ontario White, Asian and Black women were observed. Individualized counseling regarding appropriate GWG is universally recommended. Additional consideration of racial/ethnic variations by maternal weight classes may help to promote healthy GWG in Canada.

Objectives: To explore provincial variation in both excess and inadequate pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) and their impact on small- and large-for-gestational-age (SGA, LGA) infants., Methods: Four provinces with a perinatal database capturing the required exposures participated: British Columbia (BC), Ontario (ON), Nova Scotia (NS), and Newfoundland and Labrador (NL). In multiple, concurrent retrospective studies, we included women ≥ 19 years, who gave birth from 22 +0 to 42 +6  weeks' gestation, to a live singleton from April 2013-March 2014. From adjusted odds ratios, we calculated population attributable fractions (PAF) of SGA and LGA for BMI and GWG., Results: The proportion of overweight and obese women increased from western to eastern Canada. In BC, ON, NS, and NL, the proportions of women who were overweight were 21.1%, 24.0%, 23.7%, and 25.4%, while obesity proportions were 14.2%, 18.1%, 24.2%, and 29.8%, respectively. Excess GWG affected 53.9%, 49.9%, 57.6%, and 65.6% of women, respectively. Excess GWG contributed to 29.5-42.5% of LGA, compared with the PAFs for overweight (6.8-12.0%) and obesity (13.2-20.6%). Inadequate GWG's contribution to SGA (4.8-12.3%) was higher than underweight BMI's (2.9-6.2%)., Conclusion: In this interprovincial study, high and increasing proportions of women from west to east had excess pre-pregnancy BMI, and between half to two thirds had excess GWG. The contributions of GWG outside of recommendations to SGA and LGA were greater than that of low or high BMI. GWG is a potentially modifiable determinant of SGA and LGA across Canada.