Platelet membrane biomimetic nanoparticle-targeted delivery of TGF-ß1 siRNA attenuates renal inflammation and fibrosis.

The progression of renal fibrosis to end-stage renal disease (ESRD) is significantly influenced by transforming growth factor-beta (TGF-beta) signal pathway. This study aimed to develop nanoparticles (PMVs@PLGA complexes) with platelet membrane camouflage, which can transport interfering RNA to target and regulate the TGF-ß1 pathway in damaged renal tissues. The aim is to reduce the severity of acute kidney injury and to reduce fibrosis in chronic kidney disease. Hence, we formulated PMVs@TGF-ß1-siRNA NP complexes and employed them for both in vitro and in vivo therapy. From the experimental findings we know that the PMVs@siRNA NPs could effectively target the kidneys in unilateral ureteral obstruction (UUO) mice and ischemia/reperfusion injury (I/R) mice. In animal models of treatment, PMVs@siRNA NP complexes effectively decreased the expression of TGF-ß1 and mitigated inflammation and fibrosis in the kidneys by blocking the TGF-ß1/Smad3 pathway. Therefore, these PMVs@siRNA NP complexes can serve as a promising biological delivery system for treating kidney diseases.

Current Status and Influencing Factors of Secondary Traumatic Stress in Emergency and Intensive Care nurses:A Cross-Sectional Analysis.

Objective: Secondary traumatic stress (STS) is stress caused by helping or wanting to help someone who has suffered a traumatic event. STS has adverse effects on nurses and their work, such as reduced career achievement, an increased staff turnover rate, inability to complete work, avoidance of contact with patients, mental exhaustion, negative emotions which seriously affect the quality of their work and life. The study to investigate secondary traumatic stress in emergency and intensive care nurses and analyze factors that influence it. Material and Methods: The study was a cross-sectional survey. Convenience sampling was used to select hospital emergency and intensive care department nurses (n=434) who met the inclusion and exclusion criteria from August to October 2021 to participate in this study. They provided demographic data and completed measures of secondary traumatic stress, emotional intelligence, anxiety and depression. Data analysis included independent samples t-tests, one-way analysis of variance, Pearson correlation analysis and multiple linear regression analysis. Results: Almost one-third (30.7%) of participants were at moderate risk for Secondary Traumatic Stress Scale or above, with high average scores on measures of anxiety (GAD-7 average = 6.05 ± 4.13), and depression (PHQ-9 average = 6.35 ± 4.85). The results of multiple linear regression analysis showed that the average daily amount of sleep in the past week, the number of night shifts in the past month, emotional intelligence, anxiety, and depression influenced secondary traumatic stress, explaining 70.8% of the variance. Conclusion: The STS of emergency and intensive care nurses in Changzhou is at a high level. Sleep time, number of night shifts and emotional intelligence are related to secondary traumatic stress and anxiety and depression significantly predicted the degree of secondary traumatic stress. Nurses need to master effective treatment methods for secondary traumatic stress, to improve their work efficiency and nursing quality and ensure nursing safety.

CARE as a wearable derived feature linking circadian amplitude to human cognitive functions.

Circadian rhythms are crucial for regulating physiological and behavioral processes. Pineal hormone melatonin is often used to measure circadian amplitude but its collection is costly and time-consuming. Wearable activity data are promising alternative, but the most commonly used measure, relative amplitude, is subject to behavioral masking. In this study, we firstly derive a feature named circadian activity rhythm energy (CARE) to better characterize circadian amplitude and validate CARE by correlating it with melatonin amplitude (Pearson's r = 0.46, P = 0.007) among 33 healthy participants. Then we investigate its association with cognitive functions in an adolescent dataset (Chinese SCHEDULE-A, n = 1703) and an adult dataset (UK Biobank, n = 92,202), and find that CARE is significantly associated with Global Executive Composite (ß = 30.86, P = 0.016) in adolescents, and reasoning ability, short-term memory, and prospective memory (OR = 0.01, 3.42, and 11.47 respectively, all P < 0.001) in adults. Finally, we identify one genetic locus with 126 CARE-associated SNPs using the genome-wide association study, of which 109 variants are used as instrumental variables in the Mendelian Randomization analysis, and the results show a significant causal effect of CARE on reasoning ability, short-term memory, and prospective memory (ß = -59.91, 7.94, and 16.85 respectively, all P < 0.0001). The present study suggests that CARE is an effective wearable-based metric of circadian amplitude with a strong genetic basis and clinical significance, and its adoption can facilitate future circadian studies and potential intervention strategies to improve circadian rhythms and cognitive functions.

FuBay: An Integrated Fusion Framework for Hyperspectral Super-Resolution Based on Bayesian Tensor Ring.

Fusion with corresponding finer-resolution images has been a promising way to enhance hyperspectral images (HSIs) spatially. Recently, low-rank tensor-based methods have shown advantages compared with other kind of ones. However, these current methods either relent to blind manual selection of latent tensor rank, whereas the prior knowledge about tensor rank is surprisingly limited, or resort to regularization to make the role of low rankness without exploration on the underlying low-dimensional factors, both of which are leaving the computational burden of parameter tuning. To address that, a novel Bayesian sparse learning-based tensor ring (TR) fusion model is proposed, named as FuBay. Through specifying hierarchical sprasity-inducing prior distribution, the proposed method becomes the first fully Bayesian probabilistic tensor framework for hyperspectral fusion. With the relationship between component sparseness and the corresponding hyperprior parameter being well studied, a component pruning part is established to asymptotically approaching true latent rank. Furthermore, a variational inference (VI)-based algorithm is derived to learn the posterior of TR factors, circumventing nonconvex optimization that bothers the most tensor decomposition-based fusion methods. As a Bayesian learning methods, our model is characterized to be parameter tuning-free. Finally, extensive experiments demonstrate its superior performance when compared with state-of-the-art methods.

Identification and characterization of ι-carrageenase from macroalgae-associated bacterium Microbulbifer sp. YNDZ01.

BACKGROUND: In the present study, the ι-carrageenase gene, Car1293, was obtained from the genome of Microbulbifer sp. YNDZ01, which was isolated from the surface of macroalgae. To date, there are few studies on ι-carrageenase and the anti-inflammatory activity of ι-carrageenan oligosaccharides (CGOS). To enhance our perspective on ι-carrageenase and ι-carrageen oligosaccharides, the sequence, protein structure, enzymatic properties, enzymatic digestion products and anti-inflammatory activity of the gene were investigated. RESULTS: The gene length of Car1293 is 2,589 bp, encoding an enzyme with 862 amino acids, which shares 34% similarity with any previously reported ι-carrageenase. The spatial structure of Car1293 consists of many α-helices with a ß-fold binding module located at its terminus, and eight binding sites were found in the binding module as a result of docking with CGOS-DP4 ligand. The optimum temperature and pH for the activity of recombinant Car1293 toward ι-carrageenan were 50 °C and 6.0, respectively. The hydrolysates of Car1293 are mainly degree of polymerization (DP)8, with minor products showing DP2, DP4, and DP6. The enzymatic hydrolysates CGOS-DP8 showed prominent anti-inflammatory activity, which was greater than that of the positive control l-monomethylarginine in lipopolysaccharide-induced RAW264.7 macrophages. It inhibited nitric oxide production, as well as significantly inhibited tumor necrosis factor-α and interleukin-6 secretion. CONCLUSION: The ι-carrageenase sequence encoded by Car1293 is novel and can hydrolyze carrageenan into CGOS-DP8 that has a significant anti-inflammatory effect. The present study fills a gap in the research on the biological activity of oligosaccharides in ι-carrageenan and provides promising data for the development of natural anti-inflammatory agent. © 2023 Society of Chemical Industry.

NDUFV1 attenuates renal ischemia-reperfusion injury by improving mitochondrial homeostasis.

Impaired mitochondrial function and dysregulated energy metabolism have been shown to be involved in the pathological progression of kidney diseases such as acute kidney injury (AKI) and diabetic nephropathy. Hence, improving mitochondrial function is a promising strategy for treating renal dysfunction. NADH: ubiquinone oxidoreductase core subunit V1 (NDUFV1) is an important subunit of mitochondrial complex I. In the present study, we found that NDUFV1 was reduced in kidneys of renal ischemia/reperfusion (I/R) mice. Meanwhile, renal I/R induced kidney dysfunction as evidenced by increases in BUN and serum creatinine, severe injury of proximal renal tubules, oxidative stress, and cell apoptosis. All these detrimental outcomes were attenuated by increased expression of NDUFV1 in kidneys. Moreover, knockdown of Ndufv1 aggravated cell insults induced by H2 O2 in TCMK-1 cells, which further confirmed the renoprotective roles of NDUFV1. Mechanistically, NDUFV1 improved the integrity and function of mitochondria, leading to reduced oxidative stress and cell apoptosis. Overall, our data indicate that NDUFV1 has an ability to maintain mitochondrial homeostasis in AKI, suggesting therapies by targeting mitochondria are useful approaches for dealing with mitochondrial dysfunction associated renal diseases such as AKI.

Multiple measurement analysis of resting-state fMRI for ADHD classification in adolescent brain from the ABCD study.

Attention deficit hyperactivity disorder (ADHD) is one of the most common psychiatric disorders in school-aged children. Its accurate diagnosis looks after patients' interests well with effective treatment, which is important to them and their family. Resting-state functional magnetic resonance imaging (rsfMRI) has been widely used to characterize the abnormal brain function by computing the voxel-wise measures and Pearson's correlation (PC)-based functional connectivity (FC) for ADHD diagnosis. However, exploring the powerful measures of rsfMRI to improve ADHD diagnosis remains a particular challenge. To this end, this paper proposes an automated ADHD classification framework by fusion of multiple measures of rsfMRI in adolescent brain. First, we extract the voxel-wise measures and ROI-wise time series from the brain regions of rsfMRI after preprocessing. Then, to extract the multiple functional connectivities, we compute the PC-derived FCs including the topographical information-based high-order FC (tHOFC) and dynamics-based high-order FC (dHOFC), the sparse representation (SR)-derived FCs including the group SR (GSR), the strength and similarity guided GSR (SSGSR), and sparse low-rank (SLR). Finally, these measures are combined with multiple kernel learning (MKL) model for ADHD classification. The proposed method is applied to the Adolescent Brain and Cognitive Development (ABCD) dataset. The results show that the FCs of dHOFC and SLR perform better than the others. Fusing multiple measures achieves the best classification performance (AUC = 0.740, accuracy = 0.6916), superior to those from the single measure and the previous studies. We have identified the most discriminative FCs and brain regions for ADHD diagnosis, which are consistent with those of published literature.

Development and function of natural TCR+ CD8αα+ intraepithelial lymphocytes.

The complexity of intestinal homeostasis results from the ability of the intestinal epithelium to absorb nutrients, harbor multiple external and internal antigens, and accommodate diverse immune cells. Intestinal intraepithelial lymphocytes (IELs) are a unique cell population embedded within the intestinal epithelial layer, contributing to the formation of the mucosal epithelial barrier and serving as a first-line defense against microbial invasion. TCRαß+ CD4- CD8αα+ CD8αß- and TCRγδ+ CD4- CD8αα+ CD8αß- IELs are the two predominant subsets of natural IELs. These cells play an essential role in various intestinal diseases, such as infections and inflammatory diseases, and act as immune regulators in the gut. However, their developmental and functional patterns are extremely distinct, and the mechanisms underlying their development and migration to the intestine are not fully understood. One example is that Bcl-2 promotes the survival of thymic precursors of IELs. Mature TCRαß+ CD4- CD8αα+ CD8αß- IELs seem to be involved in immune regulation, while TCRγδ+ CD4- CD8αα+ CD8αß- IELs might be involved in immune surveillance by promoting homeostasis of host microbiota, protecting and restoring the integrity of mucosal epithelium, inhibiting microbiota invasion, and limiting excessive inflammation. In this review, we elucidated and organized effectively the functions and development of these cells to guide future studies in this field. We also discussed key scientific questions that need to be addressed in this area.

Complete genome sequence of the denitrifying Pseudomonas sp. strain DNDY-54 isolated from deep-sea sediment of ninety east ridge.

Pseudomonas sp. strain DNDY-54, a denitrifying bacterium, was isolated from a deep-sea sediment sample from Ninety East Ridge in the Indian Ocean. Here, we show that the complete genome of DNDY-54 has one circular chromosome of 4,412,895 bp with mean 60.57% GC content. The complete genome contains 4111 predicted protein-coding genes, 59 tRNAs, and 4 rRNA operons as 16S-23S-5S rRNA. On the basis of the annotation results, we identified genes that encode 27 proteins related to nitrogen metabolism, including enzymes that make up a complete denitrifying pathway. This work will improve the understanding of nitrogen cycling in the deep biosphere and provides a new candidate for protection of the environment and applications in waste water disposal.

Effects of the information-knowledge-attitude-practice nursing model combined with predictability intervention on patients with cerebrovascular disease.

BACKGROUND: Cerebrovascular disease (CVD) poses a serious threat to human health and safety. Thus, developing a reasonable exercise program plays an important role in the long-term recovery and prognosis for patients with CVD. Studies have shown that predictive nursing can improve the quality of care and that the information -knowledge-attitude-practice (IKAP) nursing model has a positive impact on patients who suffered a stroke. Few studies have combined these two nursing models to treat CVD. AIM: To explore the effect of the IKAP nursing model combined with predictive nursing on the Fugl-Meyer motor function (FMA) score, Barthel index score, and disease knowledge mastery rate in patients with CVD. METHODS: A total of 140 patients with CVD treated at our hospital between December 2019 and September 2021 were randomly divided into two groups, with 70 patients in each. The control group received routine nursing, while the observation group received the IKAP nursing model combined with predictive nursing. Both groups were observed for self-care ability, motor function, and disease knowledge mastery rate after one month of nursing. RESULTS: There was no clear difference between the Barthel index and FMA scores of the two groups before nursing (P > 0.05); however, their scores increased after nursing. This increase was more apparent in the observation group, and the difference was statistically significant (P < 0.05). The rates of disease knowledge mastery, timely medication, appropriate exercise, and reasonable diet were significantly higher in the observation group than in the control group (P < 0.05). The satisfaction rate in the observation group (97.14%) was significantly higher than that in the control group (81.43%; P < 0.05). CONCLUSION: The IKAP nursing model, combined with predictive nursing, is more effective than routine nursing in the care of patients with CVD, and it can significantly improve the Barthel index and FMA scores with better knowledge acquisition, as well as produce high satisfaction in patients. Moreover, they can be widely used in the clinical setting.

Sex-specific genetic association between psychiatric disorders and cognition, behavior and brain imaging in children and adults.

Although there are pronounced sex differences for psychiatric disorders, relatively little has been published on the heterogeneity of sex-specific genetic effects for these traits until very recently for adults. Much less is known about children because most psychiatric disorders will not manifest until later in life and existing studies for children on psychiatric traits such as cognitive functions are underpowered. We used results from publicly available genome-wide association studies for six psychiatric disorders and individual-level data from the Adolescent Brain Cognitive Development (ABCD) study and the UK Biobank (UKB) study to evaluate the associations between the predicted polygenic risk scores (PRS) of these six disorders and observed cognitive functions, behavioral and brain imaging traits. We further investigated the mediation effects of the brain structure and function, which showed heterogeneity between males and females on the correlation between genetic risk of schizophrenia and fluid intelligence. There was significant heterogeneity in genetic associations between the cognitive traits and psychiatric disorders between sexes. Specifically, the PRSs of schizophrenia of boys showed stronger correlation with eight of the ten cognitive functions in the ABCD data set; whereas the PRSs of autism of females showed a stronger correlation with fluid intelligence in the UKB data set. Besides cognitive traits, we also found significant sexual heterogeneity in genetic associations between psychiatric disorders and behavior and brain imaging. These results demonstrate the underlying early etiology of psychiatric disease and reveal a shared and unique genetic basis between the disorders and cognition traits involved in brain functions between the sexes.

Complete genome sequence of Polaribacter sejongensis NJDZ03 exhibiting diverse macroalgal polysaccharide-degrading activity.

A macroalgal polysaccharide-degrading bacterial strain, Polaribacter sejongensis NJDZ03, was isolated from the surface of a species of Desmarestia, a seaweed genus endemic to Antarctica. To explore the mechanism underlying the multiple polysaccharide-degrading abilities of this strain, we sequenced and analyzed its complete genome. We found that the genome comprises a 4,078,668 bp circular chromosome containing 3484 coding genes, including 18 rRNA operons whose genes are arranged in the order of 16S-23S-5S rRNA. Gene annotation revealed the existence of three putative polysaccharide utilization loci (PULs) consisting of several agarase, carrangeenase, and alginate lyase genes, repectively. These PULs are likely responsible for the strong agar-, alginate-, and carrageenan-degrading capabilities of P. sejongensis NJDZ03, especially its ability to degrade diverse carrageenans, including κ-carrageenan, τ-carrageenan, and λ-carrageenan. Our findings should provide new insights into the carbon cycle of the Antarctic oceanic ecosystem.

Mannose Treatment: A Promising Novel Strategy to Suppress Inflammation.

High glucose and fructose intake have been proven to display pro-inflammatory roles during the progression of inflammatory diseases. However, mannose has been shown to be a special type of hexose that has immune regulatory functions. In this review, we trace the discovery process of the regulatory functions of mannose and summarize some past and recent studies showing the therapeutic functions of mannose in inflammatory diseases. We conclude that treatment with mannose can suppress inflammation by inducing regulatory T cells, suppressing effector T cells and inflammatory macrophages, and increasing anti-inflammatory gut microbiome. By summarizing all the important findings, we highlight that mannose treatment is a safe and promising novel strategy to suppress inflammatory diseases, including autoimmune disease and allergic disease.

Multifunctional alkalophilic α-amylase with diverse raw seaweed degrading activities.

Uncultured microbes are an important resource for the discovery of novel enzymes. In this study, an amylase gene (amy2587) that codes a protein with 587 amino acids (Amy2587) was obtained from the metagenomic library of macroalgae-associated bacteria. Recombinant Amy2587 was expressed in Escherichia coli BL21 (DE3) and was found to simultaneously possess α-amylase, agarase, carrageenase, cellulase, and alginate lyase activities. Moreover, recombinant Amy2587 showed high thermostability and alkali resistance which are important characteristics for industrial application. To investigate the multifunctional mechanism of Amy2587, three motifs (functional domains) in the Amy2587 sequence were deleted to generate three truncated Amy2587 variants. The results showed that, even though these functional domains affected the multiple substrates degrading activity of Amy2587, they did not wholly explain its multifunctional characteristics. To apply the multifunctional activity of Amy2587, three seaweed substrates (Grateloupia filicina, Chondrus ocellatus, and Scagassum) were digested using Amy2587. After 2 h, 6 h, and 24 h of digestion, 121.2 ± 4 µg/ml, 134.8 ± 6 µg/ml, and 70.3 ± 3.5 µg/ml of reducing sugars were released, respectively. These results show that Amy2587 directly and effectively degraded three kinds of raw seaweeds. This finding provides a theoretical basis for one-step enzymatic digestion of raw seaweeds to obtain seaweed oligosaccharides.

Multimodal MR Images-Based Diagnosis of Early Adolescent Attention-Deficit/Hyperactivity Disorder Using Multiple Kernel Learning.

Attention-deficit/hyperactivity disorder (ADHD) is one of the most common brain diseases among children. The current criteria of ADHD diagnosis mainly depend on behavior analysis, which is subjective and inconsistent, especially for children. The development of neuroimaging technologies, such as magnetic resonance imaging (MRI), drives the discovery of brain abnormalities in structure and function by analyzing multimodal neuroimages for computer-aided diagnosis of brain diseases. This paper proposes a multimodal machine learning framework that combines the Boruta based feature selection and Multiple Kernel Learning (MKL) to integrate the multimodal features of structural and functional MRIs and Diffusion Tensor Images (DTI) for the diagnosis of early adolescent ADHD. The rich and complementary information of the macrostructural features, microstructural properties, and functional connectivities are integrated at the kernel level, followed by a support vector machine classifier for discriminating ADHD from healthy children. Our experiments were conducted on the comorbidity-free ADHD subjects and covariable-matched healthy children aged 9-10 chosen from the Adolescent Brain and Cognitive Development (ABCD) study. This paper is the first work to combine structural and functional MRIs with DTI for early adolescents of the ABCD study. The results indicate that the kernel-level fusion of multimodal features achieves 0.698 of AUC (area under the receiver operating characteristic curves) and 64.3% of classification accuracy for ADHD diagnosis, showing a significant improvement over the early feature fusion and unimodal features. The abnormal functional connectivity predictors, involving default mode network, attention network, auditory network, and sensorimotor mouth network, thalamus, and cerebellum, as well as the anatomical regions in basal ganglia, are found to encode the most discriminative information, which collaborates with macrostructure and diffusion alterations to boost the performances of disorder diagnosis.

Expression and Characterization of a Thermostable Carrageenase From an Antarctic Polaribacter sp. NJDZ03 Strain.

The complete genome of Polaribacter sp. NJDZ03, which was isolated from the surface of Antarctic macroalgae, was analyzed by next-generation sequencing, and a putative carrageenase gene Car3206 was obtained. Car3206 was cloned and expressed in Escherichia coli BL21(DE3). After purification by Ni-NTA chromatography, the recombinant Car3206 protein was characterized and the antioxidant activity of the degraded product was investigated. The results showed that the recombinant plasmid pet-30a-car3206 was highly efficiently expressed in E. coli BL21(DE3). The purified recombinant Car3206 showed a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, with an apparent molecular weight of 45 kDa. The optimum temperature of the recombinant Car3206 was 55°C, and it maintain 60-94% of its initial activity for 4-12 h at 55°C. It also kept almost 70% of the initial activity at 30°C, and more than 40% of the initial activity at 10°C. These results show that recombinant Car3206 had good low temperature resistance and thermal stability properties. The optimum pH of recombinant Car3206 was 7.0. Car3206 was activated by Na+, K+, and Ca2+, but was significantly inhibited by Cu2+ and Cr2+. Thin-layer chromatographic analysis indicated that Car3206 degraded carrageenan generating disaccharides as the only products. The antioxidant capacity of the degraded disaccharides in vitro was investigated and the results showed that different concentrations of the disaccharides had similar scavenging effects as vitamin C on O 2 • - , •OH, and DPPH•. To our knowledge, this is the first report about details of the biochemical characteristics of a carrageenase isolated from an Antarctic Polaribacter strain. The unique characteristics of Car3206, including its low temperature resistance, thermal stability, and product unity, suggest that this enzyme may be an interesting candidate for industrial processes.

Prokaryotic Diversity and Composition of Sediments From Prydz Bay, the Antarctic Peninsula Region, and the Ross Sea, Southern Ocean.

The V3-V4 hypervariable regions of the 16S ribosomal RNA gene were analyzed to assess prokaryotic diversity and community compositions within 19 surface sediment samples collected from three different regions (depth: 250-3,548 m) of Prydz Bay, the Antarctic Peninsula region, and the Ross Sea. In our results, we characterized 1,079,709 clean tag sequences representing 43,227 operational taxonomic units (OTUs, 97% similarity). The prokaryotic community distribution exhibited obvious geographical differences, and the sequences formed three distinct clusters according to the samples' origins. In general, the biodiversity of Prydz Bay was higher than those of the Antarctic Peninsula region and the Ross Sea, and there were similar prokaryotic communities in different geographic locations. The most dominant clades in the prokaryotic communities were Proteobacteria, Bacteroidetes, Thaumarchaeota, Oxyphotobacteria, Deinococcus-Thermus, Firmicutes, Acidobacteria, Fusobacteria, and Planctomycetes, but unique prokaryotic community compositions were found in each of the sampling regions. Our results also demonstrated that the prokaryotic diversity and community distribution were mainly influenced by geographical and physicochemical factors, such as Zn, V, Na, K, water depth, and especially geographical distance (longitude variation of sample location) and Ba ion content. Moreover, geochemical factors such as nutrient contents (TC, P, and Ca) also played important roles in prokaryotic diversity and community distribution. This represents the first report that Ba ion content has an obvious effect on prokaryotic diversity and community distribution in Southern Ocean sediments.

Overexpression of circ_0021093 circular RNA forecasts an unfavorable prognosis and facilitates cell progression by targeting the miR-766-3p/MTA3 pathway in hepatocellular carcinoma.

Increasing studies have demonstrated the important roles of circular RNAs (circRNAs) in human malignancies. Nevertheless, the molecular mechanisms and functions of circRNAs in hepatocellular carcinoma (HCC) are still not fully understood. In the present study, we evaluated circ_0021093 expression in 82 pairs of HCC tissues and 5 cell lines by qRT-PCR. The clinical implications of circ_0021093 were evaluated. In addition, the viability, apoptosis, migration and invasion capacities of different HCC cells were evaluated by gain-/loss-of-function experiments. Target prediction and dual-luciferase reporter experiments were performed to identify the molecular mechanisms of circ_0021093. Upregulation of circ_0021093 was found in HCC tumor samples and cells. Additionally, upregulated circ_0021093 was related to adverse clinical characteristics and an unfavorable prognosis. Furthermore, downregulated circ_0021093 attenuated cell growth, migration and invasion but increased cell apoptosis. By contrast, ectopically expressed circ_0021093 enhanced the abovementioned malignant biological behaviors. For mechanism exploration, circ_0021093 sponges of miR-766-3p were used in HCC cells. In addition, we found that metastasis-associated protein 3 (MTA3) was a direct target of miR-766-3p and that the oncogenic function of circ_0021093 was partly dependent on the miR-766-3p/MTA3 axis according to rescue assays. In conclusion, the circ_0021093/miR-766-3p/MTA3 regulatory axis may be an effective therapeutic target for HCC.

Transcriptional regulation of Bcl-2 gene by the PR/SET domain family member PRDM10.

Bcl-2 (B-cell lymphoma 2) protein is localized in the outer membrane of mitochondria, where it plays an important role in promoting cellular survival and inhibiting the actions of pro-apoptotic proteins. PRDM10 is a member of the PR/SET family of epigenetic regulators and may play a role in development and cell differentiation. Here we show that human PRDM10 contributes to the transcriptional regulation of human Bcl-2 gene. We found that PRDM10-depletion in human cells reduced the expression of Bcl-2 protein and over-expression of PRDM10 promoted Bcl-2 protein expression. Furthermore, luciferase reporter activity of Bcl-2 gene P1 promoter was significantly increased in cells co-transfected with PRDM10, and PRDM10 was able to bind to the Bcl-2 P1 promoter in vivo. Using The Cancer Genome Atlas (TCGA) data set, we found weak positive correlation between PRDM10 and Bcl-2 in several cancer types including cancers of the breast, colon, and lung tissues. These data identify a novel function for PRDM10 protein and provide insights on the transcriptional control of Bcl-2 expression.