Alzheimer's disease (AD) is a global health problem without effective methods to alleviate the disease progression. Amyloid β-protein (Aβ) is widely accepted as a key biomarker for AD. Metabolic ...syndromes, including obesity and insulin resistance, are key high risk factors for AD. Akkermansia muciniphila (Akk), the only representative human gut microbe in the genus Verrucomicrobia, can prevent the weight gain caused by a high-fat diet, repair the damaged integrity of the intestinal epithelium barrier, reduce endotoxin levels in blood and improve insulin resistance. The aim of this study is to explore the impact of Akk administration in AD model mice in different diets.
APP/PS1 mice were fed either a normal chow diet or a high-fat diet and were treated with Akk by gavage each day for 6 months. The impacts of Akk on glucose metabolism, intestinal barrier and lipid metabolism in the mouse model of AD were determined. Changes in brain pathology and neuroethology were also analyzed.
Akk effectively reduced the fasting blood glucose and serum diamine oxidase levels, and alleviated the reduction of colonic mucus cells in APP/PS1 mice. After treatment with Akk, the APP/PS1 mice showed obviously reduced blood lipid levels, improved hepatic steatosis and scapular brown fat whitening. Moreover, Akk promoted the reduction of Aβ 40-42 levels in the cerebral cortex of APP/PS1 mice, shortened the study time and improved the completion rate in Y-maze tests.
Akk effectively improved glucose tolerance, intestine barrier dysfunction and dyslipidemia in AD model mice. Our study results suggested that Akk could delay the pathological changes in the brain and relieve impairment of spatial learning and memory in AD model mice, which provides a new strategy for prevention and treatment of AD.
Osteosarcoma (OS) is the most common primary malignant bone tumor in children and adolescents, which is characterized by dysfunctional autophagy and poor differentiation. Our recent studies have ...suggested that the tripartite motif containing-21 (TRIM21) plays a crucial role in regulating OS cell senescence and proliferation via interactions with several proteins. Yet, its implication in autophagy and differentiation in OS is largely unknown. In the present study, we first showed that TRIM21 could promote OS cell autophagy, as determined by the accumulation of LC3-II, and the degradation of cargo receptor p62. Further, we were able to identify that Annexin A2 (ANXA2), as a novel interacting partner of TRIM21, was critical for TIRM21-induced OS cell autophagy. Although TRIM21 had a negligible effect on the mRNA and protein expressions of ANXA2, we did find that TRIM21 facilitated the translocation of ANXA2 toward plasma membrane (PM) in OS cells through a manner relying on TRIM21-mediated cell autophagy. This functional link has been confirmed by observing a nice co-expression of TRIM21 and ANXA2 (at the PM) in the OS tissues. Mechanistically, we demonstrated that TRIM21, via facilitating the ANXA2 trafficking at the PM, enabled to release the transcription factor EB (TFEB, a master regulator of autophagy) from the ANXA2-TFEB complex, which in turn entered into the nucleus for the regulation of OS cell autophagy. In accord with previous findings that autophagy plays a critical role in the control of differentiation, we also demonstrated that autophagy inhibited OS cell differentiation, and that the TRIM21/ANXA2/TFEB axis is implicated in OS cell differentiation through the coordination with autophagy. Taken together, our results suggest that the TRIM21/ANXA2/TFEB axis is involved in OS cell autophagy and subsequent differentiation, indicating that targeting this signaling axis might lead to a new clue for OS treatment.
Luteolin (LUT) is a naturally occurring compound found in a various of plants. Few recent studies have reported LUT antimicrobial activities against bacterial pathogens, however, the fundamental LUT ...mediated antimicrobial mechanism has never been elucidated. This study aimed to investigate the antimicrobial activities of LUT and its mode of action against Staphylococcus aureus and Listeria monocytogenes, either as planktonic cells or as biofilms. Here, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC) of LUT against S. aureus and L. monocytogenes were determined using the broth microdilution method, and the antimicrobial mode of LUT was elucidated by evaluating the variations in both cell membrane integrity and cell morphology. Moreover, the biofilm inhibition was measured by crystal violet staining assay, while its qualitative imaging was achieved by confocal laser scanning microscope and field emission scanning electron microscope. MIC and MBC values of LUT against S. aureus were 16–32 and 32–64 μg/mL, and 32–64 and 64–128 μg/mL for L. monocytogenes. LUT destroyed the cell membrane integrity, as evidenced by a significant increase in the number of non-viable cells, and well-defined variations in cell morphology. Moreover, LUT presented robust inhibitory effects on the biofilm formation, enhanced antibiotics diffusion within biofilms and killed efficiently mono- and dual-species biofilm cells. Overall, LUT demonstrates potent antimicrobial properties on planktonic and biofilm cells, and the biofilm formation, and thus has the potential use as a natural food preservative in foods.
•The antimicrobial and antibiofilm activity of luteolin against S. aureus and L. monocytogenes was investigated.•Luteolin presents impairment effect on S. aureus and L. monocytogenes cell membrane.•Luteolin restrains biofilm formation of S. aureus and L. monocytogenes.•Luteolin can kill biofilm cells of S. aureus and L. monocytogenes.
Lung cancer is the leading cause of cancer-related deaths worldwide. Tumor suppressor genes remain to be systemically identified for lung cancer. Through the genome-wide screening of ...tumor-suppressive transcription factors, we demonstrate here that GATA4 functions as an essential tumor suppressor in lung cancer in vitro and in vivo. Ectopic GATA4 expression results in lung cancer cell senescence. Mechanistically, GATA4 upregulates multiple miRNAs targeting TGFB2 mRNA and causes ensuing WNT7B downregulation and eventually triggers cell senescence. Decreased GATA4 level in clinical specimens negatively correlates with WNT7B or TGF-β2 level and is significantly associated with poor prognosis. TGFBR1 inhibitors show synergy with existing therapeutics in treating GATA4-deficient lung cancers in genetically engineered mouse model as well as patient-derived xenograft (PDX) mouse models. Collectively, our work demonstrates that GATA4 functions as a tumor suppressor in lung cancer and targeting the TGF-β signaling provides a potential way for the treatment of GATA4-deficient lung cancer.
Detection of nitro pollutants is an important topic in environmental protection. A total of 3 Cd (II) complexes (1–3) based on 3 soft organic isomers, n-(3,5-dicarboxylato benzyloxy) benzoic acid (n ...= 2, 3 or 4-H3DBB), and a linear N-donor ligand, 3-bis(imidazole-l-ylmethyl) benzene (3-bibz), have been synthesized hydrothermally. Structural diversity of Complexes 1–3 displays the architectural 2D or 3D change: Complex 1 exhibits a 2D network featuring tri-nuclear metal units, Complex 2 is a 3D framework based on similar tri-nuclear metal units, and Complex 3 shows a 3D network with binuclear units. Fluorescent sensing properties exhibited in all these complexes have been discovered to detect nitrobenzene (NB) selectively and sensitively. In particular, Complex 3 possesses high sensitivity for NB with the lowest detection limit of 1.15 × 10−10 M. The results of the theoretical calculation verified the fluorescence detection mechanism of NB by these Cd-based complexes. Therefore, these Cd-based complexes might be used as excellent luminescent sensors for NB.
Abstract
Translation is a key regulatory step, linking transcriptome and proteome. Two major methods of translatome investigations are RNC-seq (sequencing of translating mRNA) and Ribo-seq (ribosome ...profiling). To facilitate the investigation of translation, we built a comprehensive database TranslatomeDB (http://www.translatomedb.net/) which provides collection and integrated analysis of published and user-generated translatome sequencing data. The current version includes 2453 Ribo-seq, 10 RNC-seq and their 1394 corresponding mRNA-seq datasets in 13 species. The database emphasizes the analysis functions in addition to the dataset collections. Differential gene expression (DGE) analysis can be performed between any two datasets of same species and type, both on transcriptome and translatome levels. The translation indices translation ratios, elongation velocity index and translational efficiency can be calculated to quantitatively evaluate translational initiation efficiency and elongation velocity, respectively. All datasets were analyzed using a unified, robust, accurate and experimentally-verifiable pipeline based on the FANSe3 mapping algorithm and edgeR for DGE analyzes. TranslatomeDB also allows users to upload their own datasets and utilize the identical unified pipeline to analyze their data. We believe that our TranslatomeDB is a comprehensive platform and knowledgebase on translatome and proteome research, releasing the biologists from complex searching, analyzing and comparing huge sequencing data without needing local computational power.
•Precision of prediction estimated from hierarchical Bayesian model governs attentional deployment under dynamic environment.•Bayesian belief updating underlying attentional allocation is reflected ...in alpha oscillations.•Precision-dependent attention modulates alpha band activity in high-predictability and valid conditions.
In a dynamic environment, expectations of the future constantly change based on updated evidence and affect the dynamic allocation of attention. To further investigate the neural mechanisms underlying attentional expectancies, we employed a modified Central Cue Posner Paradigm in which the probability of cues being valid (that is, accurately indicated the upcoming target location) was manipulated. Attentional deployment to the cued location (α), which was governed by precision of predictions on previous trials, was estimated using a hierarchical Bayesian model and was included as a regressor in the analyses of electrophysiological (EEG) data. Our results revealed that before the target appeared, alpha oscillations (8∼13 Hz) for high-predictability cues (88 % valid) were significantly predicted by precision-dependent attention (α). This relationship was not observed under low-predictability conditions (69 % and 50 % valid cues). After the target appeared, precision-dependent attention (α) correlated with alpha band oscillations only in the valid cue condition and not in the invalid condition. Further analysis under conditions of significant attentional modulation by precision suggested a separate effect of cue orientation. These results provide new insights on how trial-by-trial Bayesian belief updating relates to alpha band encoding of environmentally-sensitive allocation of visual spatial attention.
Despite the significant advances in the treatment of multiple myeloma (MM), this disease is still considered incurable because of relapse and chemotherapy resistance, underscoring the need to seek ...novel therapies with different mechanisms. Anlotinib, a novel multi-targeted tyrosine kinase inhibitor (TKI), has exhibited encouraging antitumor activity in several preclinical and clinical trials, but its effect on MM has not been studied yet. In this study, we found that anlotinib exhibits encouraging cytotoxicity in MM cells, overcomes the protective effect of the bone marrow microenvironment and suppresses tumor growth in the MM mouse xenograft model. We further examined the underlying molecular mechanism and found that anlotinib provokes cell cycle arrest, induces apoptosis and inhibits multiple signaling pathways. Importantly, we identify c-Myc as a novel direct target of anlotinib. The enhanced ubiquitin proteasomal degradation of c-Myc contributes to the cell apoptosis induced by anlotinib. In addition, anlotinib also displays strong cytotoxicity against bortezomib-resistant MM cells. Our study demonstrates the extraordinary anti-MM effect of anlotinib both in vitro and in vivo, which provides solid evidence and a promising rationale for future clinical application of anlotinib in the treatment of human MM.
Background and aims
Special root structures that can dissolve insoluble phosphorus locked in soil are supposed to contribute not only to the growing status of themselves but also to the neighbouring ...plants. However, whether dauciform roots have any effect on the neighbouring plants and how does it respond to meadow degradation had not been studied.
Methods
Alpine meadows with different degradation statuses were selected and the functional traits of
Carex filispica
and the co-occurring species
Polygonum viviparum
were measured to explore their response to degradation, as well as the response of
Polygonum viviparum
to the dauciform roots of
Carex filispica
.
Results
The results showed that 1) the number of dauciform roots decreased with the intensifying degradation, positively related to available phosphorus in the soil and negatively related to the aboveground phosphorus of
Carex filispica
. 2)
Carex filispica
and
Polygonum viviparum
are similar in specific leaf area and specific root area, yet different in the phosphorus content. The available phosphorus in the soil was negatively related to the aboveground phosphorus of
Carex filispica
and positively related to that of
Polygonum viviparum
. 3) When lightly degraded, the proportion of dauciform roots had positive effects on the aboveground resource-acquiring traits of
Polygonum viviparum
, which were no longer significant at heavy degradation. 4)
Polygonum viviparum
and
Carex filispica
without dauciform roots have similar performance: a decrease of belowground carbon with the increasing degradation, and a trend toward resource conservation with the increasing proportion of dauciform roots, which did not exist in
Carex filispica
with dauciform roots.
Conclusion
Our study found that dauciform roots had a beneficial effect on the resource acquisition of their neighbouring plants. However, due to the uncontrollable nature of natural habitats, whether this effect is stable and strong enough to be performed in ecological restoration requires further lab-controlled studies.
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