ObjectiveHepatocellular carcinoma (HCC) is heterogeneous, especially in multifocal tumours, which decreases the efficacy of clinical treatments. Understanding tumour heterogeneity is critical when developing novel treatment strategies. However, a comprehensive investigation of tumour heterogeneity in HCC is lacking, and the available evidence regarding tumour heterogeneity has not led to improvements in clinical practice.DesignWe harvested 42 samples from eight HCC patients and evaluated tumour heterogeneity using whole-exome sequencing, RNA sequencing, mass spectrometry-based proteomics and metabolomics, cytometry by time-of-flight, and single-cell analysis. Immunohistochemistry and quantitative polymerase chain reactions were performed to confirm the expression levels of genes. Three independent cohorts were further used to validate the findings.ResultsTumour heterogeneity is considerable with regard to the genomes, transcriptomes, proteomes, and metabolomes of lesions and tumours. The immune status of the HCC microenvironment was relatively less heterogenous. Targeting local immunity could be a suitable intervention with balanced precision and practicability. By clustering immune cells in the HCC microenvironment, we identified three distinctive HCC subtypes with immunocompetent, immunodeficient, and immunosuppressive features. We further revealed the specific metabolic features and cytokine/chemokine expression levels of the different subtypes. Determining the expression levels of CD45 and Foxp3 using immunohistochemistry facilitated the correct classification of HCC patients and the prediction of their prognosis.ConclusionThere is comprehensive intratumoral and intertumoral heterogeneity in all dimensions of HCC. Based on the results, we propose a novel immunophenotypic classification of HCCs that facilitates prognostic prediction and may support decision making with regard to the choice of therapy.

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MicroRNAs (miRNAs), a class of endogenous, tiny, non-coding RNAs, are master regulators of gene expression among most eukaryotes. Intracellular miRNA abundance is regulated under multiple levels of control including transcription, processing, RNA modification, RNA-induced silencing complex (RISC) assembly, miRNA-target interaction, and turnover. In this review, we summarize our current understanding of the molecular components and mechanisms that influence miRNA biogenesis, homeostasis, and degradation in plants. We also make comparisons with findings from other organisms where necessary.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by extracellular senile plaques and intracellular neurofibrillary tangles in the brain. Amyloid-β peptides (Aβ) are considered to play a critical role in the onset and progression of AD. Apigenin (4',5,7-trihydroxyflavone) is a pharmacologically active agent. Even though some evidence suggests that it has potential neuroprotective effects, no preexisting study has reported any therapeutic effects of apigenin in AD models. In the present study, we examined the effects of apigenin on cognitive function in APP/PS1 double transgenic AD mice and explored its mechanism(s) of action. Three-month oral treatment with apigenin rescued learning deficits and relieved memory retention in APP/PS1 mice. Apigenin also showed effects affecting APP processing and preventing Aβ burden due to the down-regulation of BACE1 and β-CTF levels, the relief of Aβ deposition, and the decrease of insoluble Aβ levels. Moreover, apigenin exhibited superoxide anion scavenging effects and improved antioxidative enzyme activity of superoxide dismutase and glutathione peroxidase. In addition, apigenin restored neurotrophic ERK/CREB/BDNF pathway in the cerebral cortex. In conclusion, apigenin may ameliorate AD-associated learning and memory impairment through relieving Aβ burden, suppressing amyloidogenic process, inhibiting oxidative stress, and restoring ERK/CREB/BDNF pathway. Therefore, apigenin appears to represent an alternative medication for the prevention and/or therapy of AD.

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Crops grown in heavy metal contaminated soils are an important avenue for these toxic pollutants entering the human food chain. Information on how crops respond to soil contaminations of single versus multiple metals is scarce and much needed. This study investigated the accumulation of Cd by 24 cultivars of asparagus bean (Vigna unguiculata subsp. Sesquipedalis L., family Fabaceae) under a low level (0.8 mg kg-1) and a high level (11.8 mg kg-1) of Cd exposure in a garden experiment, and that in a field experiment with Cd, Pb, and Zn (1.2, 486, and 1114 mg kg-1, respectively) contaminated soil. Both experiments showed that there were highly significant variations among the tested cultivars in Cd accumulation by roots, stems, leaves, and fruits of asparagus bean. In the garden experiment, all cultivars under the low Cd exposure and 41.7% of the tested cultivars under the high Cd exposure bore fruits (pods) whose Cd concentrations were lower than 0.05 mg kg-1 fw and therefore were safe for consumption. In addition, the fruit Cd concentrations of cultivars with black seed coats were significantly lower than those with red or spotted seed coats. These results suggest that asparagus bean is a hypo-accumulator to Cd pollutant and the trait of Cd accumulation is genetic-dependent among cultivars. In the field experiment, correlation between fruit Cd and Pb concentrations was significantly positive (p < 0.05). Additional correlation analyses between two experiments showed that fruit Cd concentrations in the field experiment were significantly correlated with those exposed to the high level of Cd stress, instead of to the low level of Cd stress in the garden experiment. This suggests that the presence of other toxic heavy metals in the soil might have facilitated the accumulation of Cd in fruits, and the selection of pollution-safe-cultivars (PSC) in multi-metal polluted condition could refer to the PSCs selected under a high level exposure of a single heavy metal.

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ObjectiveFecal calprotectin (FC) is an established biomarker of gut inflammation. The aim of this study was to evaluate FC concentrations in healthy children between 1 and 18 months of age.MethodsHealthy children aged 1-18 months were enrolled in this study at the Department of Children's Health Care in Shanghai, China. Children’s stool samples were collected and analyzed, and FC concentration was determined using a commercially available enzyme-linked immunosorbent assay (ELISA). The children's weights and lengths were measured. Parents were asked to complete a brief questionnaire regarding several clinical and sociodemographic factors.ResultsThe FC concentrations were unevenly distributed; the median FC concentration was 174.3 μg/g (range: 6.0-1097.7 μg/g) or 2.241 log10 μg/g (range: 0.775-3.041 log10 μg/g) for all 288 children. The children were divided into several age groups: 1-3 months, 3-6 months, 6-9 months, 9-12 months and 12-18 months. The median FC concentrations for these age groups were 375.2 μg/g (2.574 log10 μg/g), 217.9 μg/g (2.338 log10 μg/g), 127.7 μg/g (2.106 log10 μg/g), 96.1 μg/g (1.983 log10 μg/g) and 104.2 μg/g (2.016 log10 μg/g), respectively. A significant correlation between age and FC concentration was found (r=-0.490, p<0.001). A simple correlation analysis of weight-for-length Z-scores or weight-for-age Z-scores vs. FC concentrations showed that these variables were negatively correlated (Spearman’s rho=-0.287, p<0.001; Spearman’s rho=-0.243, p<0.001, respectively).ConclusionsThe FC levels of children aged 1-18 months exhibit a downward trend with increasing age and are greater than the normal levels observed in healthy adults. In healthy children aged <6 months, FC levels are high. In children aged 6-18 months, FC concentrations are relatively low but are still higher than those of children aged >4 years.