Hydrogels as flexible sensor have attracted significant attention due to its conductivity, stretchability and flexibility. However, it is still a great challenge to prepare hydrogels that ...simultaneously possess high strength, anti-fatigue, self-adhesion, and anti-freezing. Herein, a multifunctional dual-network hydrogel was prepared by in situ polymerization of acrylic monomer in chitosan chains, and coordinated with aluminum chloride and glycerol. Based on chain entanglement, hydrogen bonding and coordination interactions, this dual-network hydrogel exhibited excellent mechanical properties, good fatigue resistance, and excellent adhesion performance. It can be used as a strain sensor for its stable conductivity and high sensitivity, which could monitor both large human motions and subtle motions. Due to the presence of glycerol, the hydrogel showed outstanding freezing resistance and still kept flexible and conductive even at low temperatures (−20 °C). This hydrogel can be applied as a flexible wearable sensor for monitoring human motion in extreme low-temperature condition.
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Contrast-induced acute kidney injury (CI-AKI) is the third most common cause of hospital-acquired renal failure. However, there is no effective treatment of CI-AKI, and its mechanism is unknown. ...Interestingly, atorvastatin has been reported to be effective in renal injury. Therefore, the aim of this study was to explore the effect and possible molecular mechanism of atorvastatin in CI-AKI.
On the CI-AKI in vitro model, rat tubular epithelial cells (NRK-52E) were treated with 18 mg I/ml meglumine diatrizoate (MEG) and then pretreated with atorvastatin. pcDNA3.1-TLR4 treatment was performed to overexpress toll-like receptor 4 (TLR4) in NRK-52E cells. Cell Counting Kit-8 (CCK-8) and lactate dehydrogenase (LDH) kits were used to detect NRK-52E cell viability as well as LDH release in each group, respectively; qRT-PCR to determine mRNA expression of TLR4 in cells; western blot to detect protein expression levels of pyroptosis-related proteins (NLRP3, caspase-1, ASC, and GSDMD) and TLR4/MyD88/NF-κB signaling pathway-related proteins (TLR4, MyD88, NF-κBp65, and p-NF-κB p65) in cells.
MEG treatment significantly inhibited the viability of NRK-52E cells, increased pro-inflammatory factor levels and promoted pyroptosis, representing successful establishment of a rat tubular epithelial cell (NRK-52E) CI-AKI in vitro model. Notably, atorvastatin increased the activity of MEG-treated NRK-52E cells and alleviated cell injury in a concentration-dependent manner. In addition, atorvastatin significantly down-regulated the expression of TLR4 in MEG-treated NRK-52E cells. However, overexpression of TLR4 inhibited the effects of atorvastatin on increasing cell viability, alleviating cell injury, reducing pro-inflammatory factors (IL-1β, IL-6, and TNF-α) levels, and inhibiting apoptosis (by down-regulating the expression of NLRP3, caspase-1, ASC, and GSDMD). Furthermore, atorvastatin also inhibited the expression of TLR4/MyD88/NF-κB pathway-related proteins (TLR4, MyD88, and p-NF-κB p65).
Atorvastatin can attenuate CI-AKI through increasing the activity of MEG-treated renal tubular epithelial cells, relieving cell injury, as well as inhibiting pyroptosis and inflammation. More importantly, the mechanism was achieved by inhibiting the TLR4//MyD88/NF-κB signaling pathway.
Aims/Introduction:
Diabetic nephropathy (DN) is one of the main complications of diabetes. Genomics may reveal the essential pathogenesis of DN. We analyzed datasets to search for key genes to ...explore pathological mechanisms of DN.
Materials and Methods:
In this study, weighted gene co-expression network analysis (WGCNA) was used to divide the differential expression genes (DEGs) from GSE142025 into different modules, and enrichment pathway analysis was conducted for each module to find key genes related to cell death pathway. Then, verification was carried out through network and histopathology. Finally, the regulatory mechanisms of key gene expression, including transcription factors (TFs), miRNA and E3 ligases related to ubiquitination, were predicted through website prediction and then miRNA results were validated using GSE51674 dataset.
Results:
The results of WGCNA and enrichment pathway analysis indicated that ferroptosis had significantly occurred in advanced DN (AND) group. Analysis of DEGs indicated that the occurrence and development of ferroptosis are mainly through ALOX15-mediated lipid metabolism pathway, which was found in all intrinsic cells of the glomerulus detected by IHC and IF staining. Moreover, network predictions were used for searching ALOX15-related TFs and ubiquitination. Meanwhile, the network predictions combining with other dataset furtherly discovered miRNAs which regulated ALOX15 expression. This study showed that the levels of mmu-miR-142-3p increased in DN mice kidney tissues, compared with the NC group.
Conclusion:
Ferroptosis existed in glomerular intrinsic cells of ADN group and its potential key candidate gene was ALOX15 which may be regulated by miR-142 and miRNA-650, TFs (CREBBP, EP300, HDAC1, MTA1, SPI1, STAT6) and E3 ligases related to ubiquitination (PML, ZMIZ1, MARCHF1, MARCHF3, MARCHF8, MARCHF11).
Purpose
To determine if magnetic resonance imaging (MRI) histogram analyses can help predict response to chemotherapy in patients with colorectal hepatic metastases by using response evaluation ...criteria in solid tumours (RECIST1.1) as the reference standard.
Materials and methods
Standard MRI including diffusion-weighted imaging (b=0, 500 s/mm
2
) was performed before chemotherapy in 53 patients with colorectal hepatic metastases. Histograms were performed for apparent diffusion coefficient (ADC) maps, arterial, and portal venous phase images; thereafter, mean, percentiles (1st, 10th, 50th, 90th, 99th), skewness, kurtosis, and variance were generated. Quantitative histogram parameters were compared between responders (partial and complete response, n=15) and non-responders (progressive and stable disease, n=38). Receiver operator characteristics (ROC) analyses were further analyzed for the significant parameters.
Results
The mean, 1st percentile, 10th percentile, 50th percentile, 90th percentile, 99th percentile of the ADC maps were significantly lower in responding group than that in non-responding group (
p
=0.000–0.002) with area under the ROC curve (AUCs) of 0.76–0.82. The histogram parameters of arterial and portal venous phase showed no significant difference (
p
>0.05) between the two groups.
Conclusion
Histogram-derived parameters for ADC maps seem to be a promising tool for predicting response to chemotherapy in patients with colorectal hepatic metastases.
Key Points
•
ADC histogram analyses can potentially predict chemotherapy response in colorectal liver metastases.
•
Lower histogram-derived parameters (mean, percentiles) for ADC tend to have good response.
•
MR enhancement histogram analyses are not reliable to predict response.
Local renin-angiotensin system (RAS) in female reproductive system is involved in many physiological and pathological processes, such as follicular development, ovarian angiogenesis, ovarian, and ...endometrial cancer progress. However, studies on the functional relevance of RAS in human endometrium are limited, especially for renin-angiotensin-aldosterone system (RAAS). In this study, we defined the location of RAS components in human endometrium. We found that angiotensin II type-1 receptor (AT
R) and aldosterone synthase (CYP11B2), major components of RAAS, are specifically expressed in endometrial gland during mid-secretory phase. Aldosterone receptor, mineralocorticoid receptor (MR), is elevated in stroma in mid-secretory endometrium. In vitro, MR is also activated by aldosterone during decidualization. Activated MR initiates LKB1 expression, followed by phosphorylating of AMPK that stimulates PDK4 expression. The impact of PDK4 on decidualization is independent on PDHE1α inactivation. Based on co-immunoprecipitation, PDK4 interacts with p-CREB to prevent its ubiquitination for facilitating decidualization via FOXO1. Restrain of MR activation interrupts LKB1/p-AMPK/PDK4/p-CREB/FOXO1 pathway induced by aldosterone, indicating that aldosterone action on decidualization is mainly dependent on MR stimulation. Aldosterone biosynthesized in endometrial gland during mid-secretory phase promotes decidualization via activating MR/LKB1/p-AMPK/PDK4/p-CREB/FOXO1 signaling pathway. This study provides the valuable information for understanding the underlying mechanism during decidualization.
The kiwifruit (Actinidia chinensis) is an economically and nutritionally important fruit crop with remarkably high vitamin C content. Here we report the draft genome sequence of a heterozygous ...kiwifruit, assembled from ~140-fold next-generation sequencing data. The assembled genome has a total length of 616.1 Mb and contains 39,040 genes. Comparative genomic analysis reveals that the kiwifruit has undergone an ancient hexaploidization event (γ) shared by core eudicots and two more recent whole-genome duplication events. Both recent duplication events occurred after the divergence of kiwifruit from tomato and potato and have contributed to the neofunctionalization of genes involved in regulating important kiwifruit characteristics, such as fruit vitamin C, flavonoid and carotenoid metabolism. As the first sequenced species in the Ericales, the kiwifruit genome sequence provides a valuable resource not only for biological discovery and crop improvement but also for evolutionary and comparative genomics analysis, particularly in the asterid lineage.
Emerging evidence suggests that epithelial‐mesenchymal transitions (EMTs) play important roles in tumor metastasis and recurrence. Understanding molecular mechanisms that regulate the EMT process is ...crucial for improving treatment of hepatocellular carcinoma (HCC). MicroRNAs (miRNAs) play important roles in HCC; however, the mechanisms by which miRNAs target the EMT and their therapeutic potential remains largely unknown. To better explore the roles of miRNAs in the EMT process, we established an EMT model in HCC cells by transforming growth factor beta 1 treatment and found that several tumor‐related miRNAs were significantly decreased. Among these miRNAs, miR‐125b expression was most strongly suppressed. We also found down‐regulation of miR‐125b in most HCC cells and clinical specimens, which correlated with cellular differentiation in HCC patients. We then demonstrated that miR‐125b overexpression attenuated EMT phenotype in HCC cancer cells, whereas knockdown of miR‐125b promoted the EMT phenotype in vitro and in vivo. Moreover, we found that miR‐125b attenuated EMT‐associated traits, including chemoresistance, migration, and stemness in HCC cells, and negatively correlated with EMT and cancer stem cell (CSC) marker expressions in HCC specimens. miR‐125b overexpression could inhibit CSC generation and decrease tumor incidence in the mouse xenograft model. Mechanistically, our data revealed that miR‐125b suppressed EMT and EMT‐associated traits of HCC cells by targeting small mothers against decapentaplegic (SMAD)2 and 4. Most important, the therapeutic delivery of synthetic miR‐125b mimics decreased the target molecule of CSC and inhibited metastasis in the mice model. These findings suggest a potential therapeutic treatment of miR‐125b for liver cancer. Conclusion: miR‐125b exerts inhibitory effects on EMT and EMT‐associated traits in HCC by SMAD2 and 4. Ectopic expression of miR‐125b provides a promising strategy to treat HCC. (Hepatology 2015;62:801–815)
Metazoan guts are in permanent contact with microbial communities. However, the host mechanisms that have developed to manage the dynamic changes of these microorganisms and maintain homeostasis ...remain largely unknown.
Serotonin (5-hydroxytryptamine 5-HT) was found to modulate gut microbiome homeostasis via regulation of a dual oxidase (Duox) gene expression in both Bactrocera dorsalis and Aedes aegypti. The knockdown of the peripheral 5-HT biosynthetic gene phenylalanine hydroxylase (TPH) increased the expression of Duox and the activity of reactive oxygen species, leading to a decrease in the gut microbiome load. Moreover, the TPH knockdown reduced the relative abundance of the bacterial genera Serratia and Providencia, including the opportunistic pathogens, S. marcescens and P. alcalifaciens in B. dorsalis. Treatment with 5-hydroxytryptophan, a precursor of 5-HT synthesis, fully rescued the TPH knockdown-induced phenotype.
The findings reveal the important contribution of 5-HT in regulating gut homeostasis, providing new insights into gut-microbe interactions in metazoans.
Monocyte to lymphocyte ratio (MLR) has been confirmed as a novel marker of poor prognosis in patients with coronary heart disease (CAD). However, the prognosis value of MLR for patients with CAD ...after percutaneous coronary intervention (PCI) needs further studies. In present study, we aimed to investigate the correlation between MLR and long-term prognosis in patients with CAD after PCI. A total of 3,461 patients with CAD after PCI at the First Affiliated Hospital of Zhengzhou University were included in the analysis. According to the cutoff value of MLR, all of the patients were divided into 2 groups: the low-MLR group (<0.34, n = 2338) and the high-MLR group (≥0.34, n = 1123). Kaplan–Meier curve was performed to compare the long-term outcome. Multivariate COX regression analysis was used to assess the independent predictors for all-cause mortality, cardiac mortality and MACCEs. Multivariate COX regression analysis showed that the high MLR group had significantly increased all-cause mortality (ACM) hazard ratio (HR) = 1.366, 95% confidence interval (CI): 1.366-3.650, p = 0.001 and cardiac mortality (CM) (HR = 2.379, 95%CI: 1.611-3,511, p < 0.001) compared to the low MLR group. And high MLR was also found to be highly associated with major adverse cardiovascular and cerebrovascular events (MACCEs) (HR = 1.227, 95%CI: 1.003-1.500, p = 0.047) in patients with CAD undergoing PCI. MLR was an independent predictor of ACM, CM and MACCEs in CAD patients who underwent PCI.
Microorganisms in anaerobic digestion (AD) are easily affected by ammonia, especially acetoclastic methanogens. Thus, in ammonia-suppressed AD systems, acetate degradation is reported to be carried ...out mainly by the cooperation of syntrophic acetate oxidizers and hydrogenotrophic methanogens. Previous studies have revealed ammonia inhibition on microbial flora by AD performance, but the effect mechanism of ammonia on microbial metabolism remains poorly understood. In this study, we constructed a mesophilic chemostat fed with acetate as the sole carbon source, gradually increased the total ammonia nitrogen (TAN) concentration from 1 g L
to 6 g L
, and employed the 16S rRNA gene, metagenomics, and metatranscriptomics analysis to characterize the microbial community structure and metabolic behavior. The results showed that even at the TAN of 6 g L
(pH 7.5), the methanogenesis kept normal, the biogas production was approximately 92% of that at TAN of 1 g L
and the acetate degradation ratio reached 99%, suggesting the strong TAN tolerance of the microbial community enriched. 16S rRNA gene analysis suggested that the microbial community structure changed along with the TAN concentration.
predominated in methanogens all the time, in which the dominant species was gradually replaced from
to
with the increased TAN. Dominant bacterial species also changed and
showed a significant positive correlation with increased TAN. Meta-omics analysis showed that the absolute dominant microorganisms at TAN of 6 g L
were
and
, both of which highly expressed genes for anti-oxidative stress.
and the second dominant methanogen
highly expressed both acetate cleavage and CO
reduction pathways, suggesting the possibility that these two pathways contributed to methanogenesis together.
and some other species in Firmicutes and Synergistetes were likely acetate oxidizers in the community as they highly expressed genes for syntrophic acetate oxidization, H
generation, and electron transfer. These results suggested that
as well as
have strong ammonia tolerance and played critical roles in acetate degradation under ammonia-suppressed conditions. The achievements of the study would contribute to the regulation and management of the AD process.
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