Gut microbiota dysbiosis plays a crucial role in the occurrence and progression of nonalcoholic fatty liver disease (NAFLD), which may be influenced by nutritional supplementation. Quinoa, a type of ...pseudocereal, has gained prominence due to its high nutritional value and diverse applications. This study aimed to determine whether yogurt containing quinoa can ameliorate NAFLD and alleviate metabolic disorders by protecting against the divergence of gut microbiota. Our findings suggested that quinoa yogurt could significantly reduce the body weight gain and fat tissue weight of high-fat diet (HFD)–fed obese mice. In addition, quinoa yogurt significantly reduced liver steatosis and enhanced glucose homeostasis and insulin sensitivity. Additional research indicates that quinoa yogurt can reduce the levels of proinflammatory cytokines (i.e., tumor necrosis factor α, IL-1β, and IL-6) and inhibit endotoxemia and systemic inflammation. The characteristics of the gut microbiota were then determined by analyzing 16S rRNA. In addition, we discovered that the gut microbiota was disturbed by HFD consumption. Particularly, intestinal probiotics and beneficial intestinal secretions were increased, leading to the expression of glucagon-like peptide-1 in the colon, contributing to NAFLD. Furthermore, endotoxemia and systemic inflammation in HFD-fed mice were restored to the level of control mice when they were fed yogurt and quinoa. Therefore, yogurt containing quinoa can effectively alleviate NAFLD symptoms and may exert its effects via microbiome-gut-liver axis mechanisms. According to some research, the role of the enteric-liver axis may also influence metabolic disorders to reduce the development of NAFLD.
•Cinnamaldehyde inhibits the production of multiple SPI-1 virulence proteins without inhibiting bacterial growth.•Cinnamaldehyde inhibits S. Typhimurium invasion into mammalian cells.•Cinnamaldehyde ...inhibits the transcription of several SPI-1 effector proteins and regulator proteins in S. Typhimurium.
The increasing understanding of bacterial pathogenesis has revealed many new targets for the development of non-traditional antibacterial drugs. Interference with bacterial virulence has become a new strategy to treat bacteria-mediated diseases. As an important food-borne pathogen, Salmonella enterica serovar Typhimurium uses type III secretion system (T3SS) to facilitate invasion of host cells. In this study, we identified cinnamaldehyde as a Salmonella pathogenicity island 1 (SPI-1) inhibitor which blocks the secretion of several SPI-1 associated effector proteins and consequently exhibits a strong inhibitory effect on SPI-1-mediated invasion of HeLa cells. Further study revealed that cinnamaldehyde significantly reduced the transcription of some SPI-1 genes, such as sipA and sipB, in S. Typhimurium by affecting multiple SPI-1 regulator genes. In an animal infection model, cinnamaldehyde effectively protected infected mice against S. Typhimurium-induced mortality and pathological damages. In summary, this study presented an effective SPI-1 inhibitor, cinnamaldehyde, which reduces the expression of SPI-1 effector proteins by regulating the transcription of main regulator genes.
Topic-specific political stance inference in social networks (SNs) aims at inferring target users' attitudes toward different target topics. Traditional methods mainly used a language model to ...classify sentiments from the postings of the SN users. However, people's stances are not always equal to their sentiments. Some others tried to build separate models toward different target topics. In many cases, though SN users talked about the target topics, the information given was limited; or they only expressed attitudes toward some other issues except the target topics. When information is incomplete, the methods that treat the topics independently fail to work, let alone for users who didn't post any of the topics. To solve the above problems, we introduced a political knowledge graph (PKG) to supplement side information for users and topics and proposed a united Knowledge Graph-aware and Social Network-enhanced framework (KGSN) to capture not only the knowledge connections between topics but also the social connections between users. KGSN utilized two levels of graph convolutional networks, the one at the knowledge graph level generating knowledge-aware representations merging knowledge entities for the users and topics respectively, and the one at the social graph level generating social-enhanced representations merging social neighbors for the target users. Beyond that, the respective topic-specific attention mechanisms were leveraged to emphasize special knowledge entities in the knowledge graph and special neighboring users in the social graph. The advantages of KGSN are that: first, it can infer users' attitudes toward more than one topic in one model; second, it can infer users' implicit attitudes toward the target topics through users' explicit attitudes toward the other issues; last but not least, even for users without any postings, KGSN can infer users' implicit attitudes through their social neighbors. Finally, extensive experiments were conducted to demonstrate the superiority of KGSN over state-of-the-art models and case studies were investigated to testify the effectiveness of the model.
Metabolic dysfunction-associated fatty liver disease (MAFLD) is a new definition for the evidence of hepatic steatosis and metabolic dysfunctions. The specific role of the dietary factors in the ...development and progress of the disease are not well illuminated. Thus, we conducted this study on the associations between dietary quality assessed by five dietary quality indexes (Dietary Inflammatory Index, DII; Mediterranean diet, MED; Dietary Approach to Stop Hypertension, DASH; Alternate Healthy Eating Index diet, AHEI; Healthy Eating Indices, HEI) and MAFLD phenotypes. This study was extracted from the latest NHANES 2017–2018 wave. Demographic information, health status, lifestyles, and dietary habits were reported in the questionnaire. Multivariate logistic regression and multivariate ordinal logistic regression methods were applied to explore the associations between dietary quality indexes and MAFLD or MAFLD with liver fibrosis. The weighted prevalence of Non-MAFLD, MAFLD without fibrosis, and MAFLD with fibrosis were 47.05%, 36.67%, and 16.28%, respectively, at the cutoff value of a median Controlled Attenuation Parameter (CAP) 248 dB/m and a median Liver Stiffness Measurement (LSM) 6.3 kPa. When the diagnostic cutoff values of CAP changed to 285 dB/m, the weighted prevalence of Non-MAFLD, MAFLD without liver fibrosis, and MAFLD with fibrosis turned to 64.62%, 22.08%, and 13.30%, respectively. All five dietary quality indexes, including DII, HEI-2015, AHEI, DASH, and MED, were all significantly associated with MAFLD phenotypes. DII was positively associated with MAFLD phenotypes, while other four dietary quality indexes, including HEI-2015, AHEI, DASH, and MED, were significantly associated with lower risk of MAFLD phenotypes. MAFLD is becoming a threatening public health concern among adult Americans and dietary quality is markedly associated with MAFLD phenotypes.
A novel plasmid-mediated resistance-nodulation-division (RND) efflux pump gene cluster tmexCD1-toprJ1 in Klebsiella pneumoniae tremendously threatens the use of convenient therapeutic options in the ...post-antibiotic era, including the "last-resort" antibiotic tigecycline.
In this work, the natural alkaloid harmaline was found to potentiate tigecycline efficacy (4- to 32-fold) against tmexCD1-toprJ1-positive K. pneumoniae, which also thwarted the evolution of tigecycline resistance. Galleria mellonella and mouse infection models in vivo further revealed that harmaline is a promising candidate to reverse tigecycline resistance. Inspiringly, harmaline works synergistically with tigecycline by undermining tmexCD1-toprJ1-mediated multidrug resistance efflux pump function via interactions with TMexCD1-TOprJ1 active residues and dissipation of the proton motive force (PMF), and triggers a vicious cycle of disrupting cell membrane integrity and metabolic homeostasis imbalance.
These results reveal the potential of harmaline as a novel tigecycline adjuvant to combat hypervirulent K. pneumoniae infections.
Rockfalls are major geological hazards threatening prestressed concrete cylinder pipes (PCCPs) in water diversion projects. To accurately assess the impact of large deformation movements of rockfalls ...on PCCPs, this study utilized the continuous–discontinuous method to investigate the dynamic response of a PCCP under a rockfall. The impact mode of rockfalls, the mechanical characteristics of PCCP, and the nonlinear-contact characteristics between soil and PCCP were considered in this study. The advantages of continuous and discontinuous numerical simulation methods were utilized to establish a continuous and discontinuous coupling model of “tube-soil-rock” considering the interaction of soil and structure. The impact mechanism and process of PCCP under the rockfall were investigated by simulating the rockfall process and analyzing its spatiotemporal evolution. The influence of PCCP under rockfalls with different heights and radii was studied to clarify the effects of these two parameters on the PCCP. Combined with a practical application example of large-scale water transfer projects, there is a tendency of center flattening under static load and dynamic impact load, and the PCCP part directly below the impact point is the most dangerous. This investigation provided a comprehensive understanding of the impact mechanism of the PCCPs under rockfall. The findings of this study have significant implications for the design of the protection engineering of PCCPs and ensuring the safe operation of water diversion projects.
Streptococcus pneumoniae (pneumococcus) is an important causative agent of acute invasive and non-invasive infections. Pneumolysin is one of a considerable number of virulence traits produced by ...pneumococcus that exhibits a variety of biological activities, thus making it a target of small molecule drug development. In this study, we aimed to evaluate the effect of morin, a natural compound that has no antimicrobial activity against S. pneumonia, is a potent neutralizer of pneumolysin-mediated cytotoxicity and genotoxicity by impairing oligomer formation, and possesses the capability of mitigating tissue damage caused by pneumococcus. These findings indicate that morin could be a potent candidate for a novel therapeutic or auxiliary substance to treat infections for which there are inadequate vaccines and that are resistant to traditional antibiotics.
At present, the resistance of New Delhi metallo-β-lactamase-1 (NDM-1) to carbapenems and cephalosporins, one of the mechanisms of bacterial resistance against β-lactam antibiotics, poses a threat to ...human health. In this work, based on the virtual ligand screen method, we found that carnosic acid (CA), a natural compound, exhibited a significant inhibitory effect against NDM-1 (IC
= 27.07 μM). Although carnosic acid did not display direct antibacterial activity, the combination of carnosic acid and meropenem still showed bactericidal activity after the loss of bactericidal effect of meropenem. The experimental results showed that carnosic acid can enhance the antibacterial activity of meropenem against
ZC-YN3. To explore the inhibitory mechanism of carnosic acid against NDM-1, we performed the molecular dynamics simulation and binding energy calculation for the NDM-1-CA complex system. Notably, the 3D structure of the complex obtained from molecular modeling indicates that the binding region of carnosic acid with NDM-1 was not situated in the active region of protein. Due to binding to the allosteric pocket of carnosic acid, the active region conformation of NDM-1 was observed to have been altered. The distance from the active center of the NDM-1-CA complex was larger than that of the free protein, leading to loss of activity. Then, the mutation experiments showed that carnosic acid had lower inhibitory activity against mutated protein than wild-type proteins. Fluorescence experiments verified the results reported above. Thus, our data indicate that carnosic acid is a potential NDM-1 inhibitor and is a promising drug for the treatment of NDM-1 producing pathogens.
This study aimed to assess the association of dietary fiber intake with serum uric acid (SUA) levels and risk of hyperuricemia (HUA) among Chinese adults using the latest nationally representative ...data. A total of 66,427 Chinese adults aged 18 years and over from the China Adult Chronic Disease and Nutrition Surveillance in 2015 were included in this study. Dietary intakes were measured with a 3-day 24 h dietary recall and the household condiment weighing method. Mixed-effect linear and logistic regression models were used to evaluate the associations of dietary fiber intake with SUA levels and risk of HUA, respectively. Compared to the lowest intake group, the coefficient and 95% confidence in the highest intake group of total fiber were −0.06 (−0.08, −0.04) (p-trend < 0.001), −0.18 (−0.2, −0.16) (p-trend < 0.001) for cereal fiber, 0.03 (0.01, 0.04) (p-trend = 0.051) for legume fiber, 0 (−0.01, 0.02) (p-trend = 0.869) for vegetable fiber and 0.01 (−0.001, 0.04) (p-trend = 0.296) for fruit fiber. The odds ratio (OR) and 95% confidence interval (CI) of HUA for the highest vs. lowest intake group of total fiber were 0.88 (0.84, 0.91) (p-trend = 0.001), 0.67 (0.63, 0.71) (p-trend < 0.001) for cereal fiber, 1.05 (1, 1.09) (p-trend = 0.248) for legume fiber, 1.01 (0.97, 1.05) (p-trend = 0.982) for vegetable fiber and 1.06 (1, 1.12) (p-trend = 0.264) for fruit fiber. Our findings suggest that consumption of total fiber and cereal fiber were significantly inversely associated with SUA levels and HUA risk among the Chinese adult population. Developing and implementing effective public education programs are urgently needed to increase the intake of dietary fiber, especially cereal fiber among Chinese adults.
Certain foods and food groups could positively or negatively impact serum uric acid (SUA) levels. However, evidence on the holistic dietary strategy to prevent and control hyperuricemia (HUA) ...development remains limited.
The aim of this research work was to explore the association of dietary approaches to stop hypertension (DASH) diet with SUA levels and odds of HUA among Chinese adults.
This research premise included 66,427 Chinese adults aged 18 and above who were part of the China Adult Chronic Disease and Nutrition Surveillance in 2015. Dietary consumptions were assessed via the household condiment weighing approach and a three-day, 24-hour dietary recall. Total fat, saturated fat, calcium, protein, potassium, cholesterol, magnesium, fiber, and sodium were all adopted to calculate the DASH score (score range, 0-9). The associations of DASH score with SUA levels and odds of HUA were evaluated using multiple linear and logistic regression models, respectively.
We established that a higher DASH score was linked with a lower SUA levels (β = - 0.11; 95% CI: - 0.12, - 0.1; p < 0.001) and odds of HUA (OR = 0.85; 95% CI: 0.83, 0.87; p < 0.001) after adjustment for age, sex, ethnicity, education status, marital status, health behaviours and health factors. The association of the DASH diet with odds of HUA was stronger among men (p-interaction = 0.009), non-Han Chinese (p-interaction< 0.001) as well as rural residents (p-interaction< 0.001).
Our results illustrate that the DASH diet was remarkably negatively with SUA levels and odds of HUA in the Chinese adult population.
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