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Abstract Background Acute respiratory distress syndrome (ARDS) is a respiratory failure syndrome that can cause many complications, impacting patients’ quality of life. Behavioral and cognitive disorders have attracted increasing attention in patients with ARDS, but its potential mechanisms are still elusive. Methods Herein we transferred the faecal microbiota from patients with ARDS caused by community-acquired pneumonia (CAP) to antibiotics-treated recipient male mice to explore the microbiota-gut-brain mechanisms. Behavioral functions of mice were evaluated by the open field test, Morris water maze and Y-maze test. The structure and composition of the gut microbiota were analyzed by using 16S rRNA sequencing analysis. Microglia, astrocyte and neuron in the cortex and hippocampus were examined via immunofluorescent staining. Results We found that the major characteristic of the intestinal flora in ARDS/CAP patients was higher abundances of Gram-negative bacteria than normal controls. The gut microbiota derived from ARDS/CAP patients promoted neuroinflammation and behavioral dysfunctions in mice. Mice who underwent fecal transplant from ARDS/CAP patients had increased systemic lipopolysaccharide (LPS), systemic inflammation, and increased colonic barrier permeability. This may adversely impact blood barrier permeability and facilitate microglia activation, astrocyte proliferation, and loss of neurons. Conclusions Our study proposes the role of the microbiota-gut-brain crosstalk on ARDS/CAP-associated behavioral impairments and suggests the gut microbiota as a potential target for the protection of brain health in ARDS patients in clinical practice.

ObjectivesTo investigate the characteristic cytokine profile of the aqueous humor in eyes with congenital cataract and pre-existing posterior capsule dysfunction (PCD).MethodsIn this cross-sectional study, the enrolled eyes with congenital cataract and PCD were included in the PCD group, while those with an intact posterior capsule were included in the control group. Demographic data and biometric parameters were recorded. The levels of 17 inflammatory factors in the aqueous humor collected from the enrolled eyes were detected using Luminex xMAP technology, and intergroup differences in the collected data were analyzed.ResultsThe PCD group comprised 41 eyes from 31 patients with congenital cataract and PCD, whereas the control group comprised 42 eyes from 27 patients with congenital cataract and an intact posterior capsule. Lens thickness was significantly thinner in the PCD group than in the control group. However, the levels of monocyte chemoattractant protein-1 (MCP-1), transforming growth factor-β2 (TGF-β2), and vascular endothelial growth factor (VEGF) were significantly higher in the PCD group than in the control group. Multivariate logistic regression confirmed that lens thickness and TGF-β2 level were independent risk factors for PCD.ConclusionA thinner lens thickness in eyes with congenital cataract and PCD could serve as a biometric feature of these eyes. The higher levels of MCP-1, TGF-β2, and VEGF in eyes with PCD indicated a change in their intraocular inflammatory microenvironment, which possibly led to cataract progression. Lens thickness and TGF-β2 level are independent risk factors for PCD.

Abstract Document-level relation extraction is a challenging task in information extraction, as it involves identifying semantic relations between entities that are dispersed throughout a document. Existing graph-based approaches often rely on simplistic methods to construct text graphs, which do not provide enough lexical and semantic information to accurately predict the relations between entity pairs. In this paper, we introduce a document-level relation extraction method called SKAMRR (Sememe Knowledge-enhanced Abstract Meaning Representation and Reasoning). First, we generate document-level abstract meaning representation graphs using rules and acquire entity nodes’ features through sufficient information propagation. Next, we construct inference graphs for entity pairs and utilize graph neural networks to obtain their representations for relation classification. Additionally, we propose the global adaptive loss to address the issue of long-tailed data. We conduct extensive experiments on four datasets DocRE, CDR, GDA, and HacRED. Our model achieves competitive results and its performance outperforms previous state-of-the-art methods on four datasets.

Objective To investigate the relationships of leukemia inhibitory factor receptor (LIFR) with cervical cancer invasion and metastasis. Methods From January 2021 to December 2022, 45 patients treated for cervical cancer and lung metastases were identified. Western blotting was used to determine the expression of Hippo–YAP signaling pathway-related proteins. Meanwhile, 40 healthy Sprague-Dawley nude mice were used and evenly randomized into two groups, which were injected with LIFR-overexpressing (study group) or normal cervical cancer cells (control group). The lung tissue of nude mice was removed for hematoxylin–eosin staining, and the number of lung cell metastases in nude mice was counted. Results The highest LIFR mRNA expression was found in paracancerous tissue, followed by cervix cancer tissue and metastatic lesions. The study group exhibited higher LIFR, P-YAP, and P-TAZ protein expression and lower YAP and TAZ protein expression than the control group. The study group had a lower number of lung metastases than the control group. Conclusion Decreased expression of LIFR and decreased phosphorylation of Hippo–YAP signaling pathway-related proteins might be the underlying mechanisms that promote lung metastasis of cervical cancer.

AimTo observe the change of capsulotomy opening diameter (COD) in aphakic eyes after primary congenital cataract removal and investigate its influencing factors.MethodsOcular parameters, including corneal diameter (CD), axial length (AL), anterior and posterior COD (ACOD, PCOD), and age at surgery were recorded at primary congenital cataract removal and secondary intraocular lens implantation. The concentrations of 15 kinds of cytokines in aqueous humor samples collected at the primary surgery were detected. The change (Δ) of COD between two surgeries were described, and its association was analyzed.ResultsFifty eyes from 33 patients with congenital cataract who underwent primary and secondary surgery were enrolled. The changes in ACOD and PCOD were not statistically significant on the whole. ΔACOD was positively correlated with ΔCD and the concentrations of PDGF-AA, VEGF and TGF-β1. The concentration of FGF-2 and the interval between two surgeries showed negative correlations with ΔACOD and ΔPCOD.ConclusionCOD in aphakic eyes kept changing after primary surgery. The positive correlation between ΔACOD and ΔCD manifested the enlargement of ACOD was influenced by lateral eye growth. Meanwhile, ΔACOD was also associated with cytokines, indicating postoperative inflammation promoted the ACOD constriction.

The charge prediction task aims to predict appropriate charges for a given legal case automatically, which still confronts some challenging problems such as performance improvement and confusing charges issue. In this paper, inspired by the impressive success of deep neural networks in legal intelligence field, we present an end-to-end framework named law article deduplication attention neural network, ADAN, to address these problems. The incorporation of hierarchical sequence encoder and attention mechanism is employed to learn better semantic representations of fact description texts. To distinguish confusing charges, we use the relevant law articles of a given case as auxiliary information, and propose a novel difference aggregation mechanism among similar law articles for extracting effective distinguishable features. The experimental results on real-world datasets show that the performance of our proposed model is significantly better than existing methods on all evaluation metrics.

The role of inulin in alleviating obesity-related disorders has been documented; yet, its underlying mechanisms still need to be further investigated. This study attempted to elucidate the causative link between the gut microbiota and the beneficial effect of inulin on obesity-related disorders via transferring the fecal microbiota from inulin-dosed mice to high-fat diet (HFD)-induced obese recipient mice. The results show that inulin supplementation can decrease body weight, fat accumulation, and systemic inflammation and can also enhance glucose metabolism in HFD-induced obese mice. Treatment with inulin reshaped the structure and composition of the gut microbiota in HFD-induced obese mice, as characterized by increases in the relative abundances of Bifidobacterium and Muribaculum and decreases in unidentified_Lachnospiraceae and Lachnoclostridium. In addition, we found that these favorable effects of inulin could be partially transferable by fecal microbiota transplantation, and Bifidobacterium and Muribaculum might be the key bacterial genera. Therefore, our results suggest that inulin ameliorates obesity-related disorders by targeting the gut microbiota.

ObjectiveGrowth hormone receptor (GHR) mediates most GH biological actions. This study is aimed to evaluate whether GHR fl/d3 polymorphism contributes to the inter-individual variability of growth and metabolism in healthy children and adolescents.MethodsA total of 4,730 students aged 6-16 years from Yixing and Suqian City in China were included in this cross-sectional study. Height and body mass index (BMI) were transformed into the form of z-score corresponding to age and gender. Logistic regression was used to evaluate the associations of GHR fl/d3 polymorphism with height, BMI, metabolic traits, and hypertension by estimating the odds ratios (ORs) and 95% confidence intervals (CIs).ResultsGHR d3 allele was inversely associated with overweight, total cholesterol (TC) and triglyceride (TG) levels (OR [95% CI] for overweight: 0.754 [0.593-0.959], P = 0.021; OR [95% CI] for TC: 0.744 [0.614-0.902], P = 0.003; OR [95% CI] for TG: 0.812 [0.654-0.998], P = 0.047). GHR d3 allele was associated with decreased odds of pre-hypertension in boys (OR [95% CI]: 0.791 [0.645-0.971], P = 0.025), but associated with increased odds of pre-hypertension and hypertension in girls (ORs [95% CIs]: 1.379 [1.106-1.719], P = 0.004; OR [95% CI]: 1.240 [1.013-1.519], P = 0.037). Interaction of GHR fl/d3 polymorphism with gender contributed to increased odds of pre-hypertension and hypertension (interactive ORs [95% CIs]: 1.735 [1.214-2.481], P = 0.003; OR [95% CI]: 1.509 [1.092-2.086], P = 0.013). Stratification analysis showed that the correlation tendencies of GHR fl/d3 polymorphism and BMI with age were different between two cities with discrepant economic development levels.ConclusionGHR fl/d3 polymorphism is associated with growth, metabolism, and hypertension in children and adolescents with the gender specificity, and the genetic effect of GHR fl/d3 may be modified by the local socioeconomic levels.

As an essential branch of artificial intelligence, recommendation systems have gradually penetrated people’s daily lives. It is the active recommendation of goods or services of potential interest to users based on their preferences. Many recommendation methods have been proposed in both industry and academia. However, there are some limitations of previous recommendation methods: (1) Most of them do not consider the cross-correlation between data. (2) Many treat the recommendation process as a one-time act and do not consider the continuity of the recommendation system. To overcome these limitations, we propose a recommendation framework based on deep reinforcement learning techniques, known as DDRCN: a deep deterministic policy gradient recommendation framework incorporating deep cross networks. We use a Deep network and a Cross network to fit the cross relationships between the data, to obtain a representation of the user interaction data. The Actor-Critic network is designed to simulate the continuous interaction behavior of users through a greedy strategy. A deep deterministic policy gradient network is also used to train the recommendation model. Finally, we conduct experiments with two publicly available datasets and find that our proposed recommendation framework outperforms the baseline approach in the recall and ranking phases of recommendations.

Traditional Chinese medicine (TCM) has been used to treat diabetes for a long time, but its application has not been widely accepted due to unstandardized product quality and complex pharmacological mechanisms. The modernization of TCM is crucial for its further development, and in recent years the metabolomics technique has largely driven its modernization. This review focuses on the application of NMR-based metabolomics in diabetic therapy using TCM. We identified a series of metabolic pathways that altered significantly after TCM treatment, providing a better understanding of the metabolic mechanisms of TCM for diabetes care.

In this retrospective analysis, we aimed to analyze the epidemic characteristics of neonatal mortality due to preterm birth at 28-36 weeks gestation in different regions from 2009 to 2018. Data were obtained from China's Under-5 Child Mortality Surveillance System (U5CMSS). The χ2 trend test, Poisson regression and the Cochran-Mantel-Haenszel method were used in this study. We found that 51.3%, 42.0% and 44.5% of neonate deaths were preterm infants, and immaturity was mainly attributed to 60.1%, 64.1% and 69.5% of these deaths, in the eastern, central and western regions, respectively. The preterm neonatal mortality rate due to immaturity dropped from 149.2, 216.5 and 339.5 in 2009 to 47.4, 83.8 and 170.1 per 100 000 live births in 2018, giving an average annual decline rate of 12.1%, 11.6% and 6.3% in the eastern, central and western regions, respectively, during the studying period. The relative risk of preterm neonatal mortality due to immaturity were 1.3 and 2.3 for the central regions and western regions in 2009-2010, ascending to 2.2 and 3.9 in 2017-2018. The proportion of preterm neonatal deaths with a gestational age

Legal judgment prediction (LJP) is a crucial task in legal intelligence to predict charges, law articles and terms of penalties based on case fact description texts. Although existing methods perform well, they still have many shortcomings. First, the existing methods have significant limitations in understanding long documents, especially those based on RNNs and BERT. Secondly, the existing methods are not good at solving the problem of similar charges and do not fully and effectively integrate the information of law articles. To address the above problems, we propose a novel LJP method. Firstly, we improve the model’s comprehension of the whole document based on a graph neural network approach. Then, we design a graph attention network-based law article distinction extractor to distinguish similar law articles. Finally, we design a graph fusion method to fuse heterogeneous graphs of text and external knowledge (law article group distinction information). The experiments show that the method could effectively improve LJP performance. The experimental metrics are superior to the existing state of the art.

A pectin/chitosan matrix-loaded curcumin film (PCCF) with a deep eutectic solvent (DES) as the solvent and plasticizer was prepared in this study. Different quantities of curcumin (identified as PCCF-0, PCCF-1, PCCF-2. PCCF-3) were loaded on the pectin/chitosan film in order to evaluate their effects on the film properties. Results showed that curcumin could interact with the pectin/chitosan matrix and form a complex three-dimensional network structure. PCCF could promote the thickness, tensile strength, thermal properties, antioxidant and antiseptic capacities, but deteriorate the light transmission and elongation at the same time. The addition of curcumin would change the color of the film, without significantly affecting the moisture content. The tensile strength of PCCF-3 reached the maximum value of 3.75 MPa, while the elongation decreased to 10%. Meanwhile, the water-resistance properties of PCCF-3 were significantly promoted by 8.6% compared with that of PCCF-0. Furthermore, PCCF showed remarkable sustained antioxidant activities in a dose-dependent manner. PCCF-3 could inhibit DPPH and ABTS free radicals by 58.66% and 29.07%, respectively. It also showed antiseptic capacity on fresh pork during storage. Therefore, curcumin addition could improve the barrier, mechanical, antioxidant and antiseptic properties of the polysaccharide-based film and PCCF has the potential to be used as a new kind of food packaging material in the food industry.

BackgroundAC3 is one of adenylyl cyclase isoforms involved in cAMP and insulin signaling pathway. Recent reports have demonstrated that the AC3 genetic polymorphisms are associated with obesity in a Swedish population. AC3 knock out mice exhibit obese when they age. These findings suggest that AC3 plays an important role in the regulation of body weight.Methodology/principal findingsIn the present study, we evaluated the association between the AC3 genetic polymorphisms and obesity in a Han Chinese population. A total of 2580 adults, including 1490 lean (BMI = 18.5-23.9), 677 overweight (BMI 24.0-27.9) and 413 obese (BMI ≥28.0) subjects were genotyped for 5 TagSNPs in the AC3 gene. Single maker association analyses indicated that SNP rs753529 was significantly associated with BMI in obese subjects (P = 0.022, OR = 0.775 95%CI = 0.623-0.963), but not in overweight subjects (P = 0.818). Multiple maker association analyses showed that the haplotype (G-G-G) constructed with SNPs rs1127568, rs7604576 and rs753529 was significantly associated with obesity (P = 0.029). Further genotyping of SNP rs753529 in 816 children, including 361 overweight subjects (BMI>P(80)) and 455 controls (BMI = P(20-50)) were performed, and no significant association with BMI was found. All tests were adjusted for age, sex, physical activity index, household income and/or diet expenses.ConclusionsThe present study provides replication evidence that the AC3 genetic polymorphisms are associated with decreased risk of obesity among adults but not in children in a Chinese Han population. The data also suggest that the AC3 genetic effects on BMI may have interaction with the factors related to ageing and environment.

Myofibrillogenesis regulator-1 (MR-1) is a novel protein involved in cellular proliferation, migration, inflammatory reaction and signal transduction. However, little information is available on the relationship between MR-1 expression and the progression of atherosclerosis. Here we report atheroprotective effects of silencing MR-1 in a model of Ang II-accelerated atherosclerosis, characterized by suppression focal adhesion kinase (FAK) and nuclear factor kappaB (NF-κB) signaling pathway, and atherosclerotic lesion macrophage content. In this model, administration of the siRNA-MR-1 substantially attenuated Ang II-accelerated atherosclerosis with stabilization of atherosclerotic plaques and inhibited FAK, Akt, mammalian target of rapamycin (mTOR) and NF-kB activation, which was associated with suppression of inflammatory factor and atherogenic gene expression in the artery. In vitro studies demonstrated similar changes in Ang II-treated vascular smooth muscle cells (VSMCs) and macrophages: siRNA-MR-1 inhibited the expression levels of proinflammatory factor. These studies uncover crucial proinflammatory mechanisms of Ang II and highlight actions of silencing MR-1 to inhibit Ang II signaling, which is atheroprotective. [ABSTRACT FROM AUTHOR]

Activation of the silent mating type information regulation 2 homolog 1 (SIRT1) has been shown consistent antiinflammatory function. However, little information is available on the function of SIRT1 during Angiotensin II (AngII)-induced atherosclerosis. Here we report atheroprotective effects of sirt1 activation in a model of AngII-accelerated atherosclerosis, characterized by suppression proinflammatory transcription factors Nuclear transcription factor (NF)-kB and Signal Transducers and Activators of Transcription. (STAT) signaling pathway, and atherosclerotic lesion macrophage content. In this model, administration of the SIRT1 agonist SRT1720 substantially attenuated AngII-accelerated atherosclerosis with decreasing blood pressure and inhibited NF-kB and STAT3 activation, which was associated with suppression of inflammatory factor and atherogenic gene expression in the artery. In vitro studies demonstrated similar changes in AngII-treated VSMCs and macrophages: SIRT1 activation inhibited the expression levels of proinflammatory factor. These studies uncover crucial proinflammatory mechanisms of AngII and highlight actions of SIRT1 activation to inhibit AngII signaling, which is atheroprotective. [ABSTRACT FROM AUTHOR]