Identification of EDNRA as the Key Biomarker for Hypercholesterolemia and Colorectal Cancer.

Some studies have investigated the role of cholesterol in the progression of colorectal cancer (CRC). However, the underlying mechanism of action is not clear. In this study, we used bioinformatics tools to elucidate the molecular mechanisms involved. We initially obtained CRC datasets from the Gene Expression Omnibus (GEO) database and hypercholesterolemia data from GeneCards and DisGeNE. Common differentially expressed genes (DEGs) were determined by using Venn diagram web tools. Next, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses using the Database for Annotation, Visualization, and Integrated Discovery (DAVID). The hub gene was identified through common expression pattern analysis and survival analysis. Finally, we conducted an immune regulatory point analysis and predicted target drugs based on the hub gene. The results of our analysis revealed 13 common DEGs, with endothelin receptor type A (EDNRA) identified as the hub gene linking hypercholesterolemia and CRC. The results of the GO analysis showed that the common DEGs were primarily associated with the G-protein coupled receptor signaling pathway, extracellular space, and receptor binding. The results of the KEGG pathway enrichment analysis indicated enrichment in pathways related to cancer and the phospholipase D signaling pathway. Additionally, we identified potential target drugs, including Podocarpus montanus, Diospyros kaki, Herba Salviae japoniae, sitaxentan, and ambrisentan. We found that EDNRA might be an underlying biomarker for both hypercholesterolemia and CRC. The predicted target drugs provide new strategies for treating CRC.

Knockdown of LAMB3 suppressed radioresistance in nasopharyngeal carcinoma via deactivating NRF2 signaling pathway.

Nasopharyngeal carcinoma (NPC) is a prevalent malignancy in Southeast Asia and Southern China. Laminin subunit beta-3 (LAMB3) has been validated to participate in diverse cancers. Nevertheless, the role and mechanism of LAMB3 in NPC remain unclear. In this study, LAMB3 expression is upregulated in NPC cells and tissues. Interestingly, knockdown of LAMB3 promoted apoptosis and reduced the radioresistance of NPC cells. Besides, shLAMB3 enhanced X-ray-induced reactive oxygen species (ROS) accumulation. Mechanically, knockdown of LAMB3 deactivated nuclear factor erythroid-2-related factor 2 (NRF2) signaling pathway via enhancing forkhead box 3 (FOXO3) expression. In rescue experiments, suppression of NRF2 signaling pathway abrogated shLAMB3-induced NPC cell apoptosis and ROS accumulation under X-ray treatment. Similarly, LAMB3 knockdown restrains NPC tumor growth and reduces radioresistance in vivo. Thus, these findings concluded that knockdown of LAMB3 enhanced apoptosis and ROS accumulation, and suppressed radioresistance in NPC via enhancing FOXO3 expression and deactivating NRF2 signaling pathway, facilitating the development of novel strategies for NPC radioresistance.

Molecular characterization of peptidoglycan recognition proteins from Mytilus coruscus.

Mytilus shows great immune resistance to various bacteria from the living waters, indicating a complex immune recognition mechanism against various microbes. Peptidoglycan recognition proteins (PGRPs) play an important role in the defense against invading microbes via the recognition of the immunogenic substance peptidoglycan (PGN). Therefore, eight PGRPs were identified from the gill transcriptome of Mytilus coruscus. The sequence features, expression pattern in various organs and larval development stages, and microbes induced expression profiles of these Mytilus PGRPs were determined. Our data revealed the constitutive expression of PGRPs in various organs with relative higher expression level in immune-related organs. The expression of PGRPs is developmentally regulated, and most PGRPs are undetectable in larvae stages. The expression level of most PGRPs was significantly increased with in vivo microbial challenges, showing strong response to Gram-positive strain in gill and digestive gland, strong response to Gram-negative strain in hemocytes, and relative weaker response to fungus in the three tested organs. In addition, the function analysis of the representative recombinant expressed PGRP (rMcPGRP-2) confirmed the antimicrobial and agglutination activities, showing the immune-related importance of PGRP in Mytilus. Our work suggests that Mytilus PGRPs can act as pattern recognition receptors to recognize the invading microorganisms and the antimicrobial effectors during the innate immune response of Mytilus.

How to Choose a Survival Period? The Impact of Antibiotic Use on OS or PFS in NSCLC Patients Treated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis.

BACKGROUND: The development of immunotherapy has dramatically changed the treatment of non-small-cell lung cancer. The negative association of antibiotics on the clinical activity of immune checkpoint inhibitors in patients with NSCLC is well known. METHODS: PubMed, Embase, and Medline databases were searched until January 11, 2020. We included retrospective studies of ICIs (e.g., PD-1, PD-L1, and CTLA-4). The clinical outcomes were progression-free survival (PFS) and overall survival (OS). Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated, and subgroup and sensitivity analyses were performed. RESULTS: Our results indicated that the use of antibiotics reduced the survival of NSCLC patients treated with ICIs. The pooled HRs of PFS and OS were HR = 1.41 (95% CI = 1.23-1.61; P < 0.001) and HR = 2.16 (95% CI = 1.79-2.60; P < 0.001). We divided the studies into 5 subgroups according to antibiotic exposure time. Subgroup analysis showed that the patients that were administered antibiotics [-60 days; 0 days] or [-30 days; 0 days] before the initiation of ICIs treatment had a poorer OS rate, whereas those patients that were administered antibiotics [0 days; 30 days] after the initiation of ICIs treatment had a poorer PFS rate. In summary, ATB treatment in patients [-60 days; +30 days] near the initiation of ICIs treatment significantly reduced the survival in NSCLC patients. CONCLUSION: Our results indicated that ATB use is negatively associated with survival in NSCLC patients treated with ICIs immunotherapy. Similar studies involving a larger sample of cases are still being published. This meta-analysis identified that the timing of ATB treatment in NSCLC patients receiving ICIs immunotherapy has different effects on the OS and PFS of these patients. ATB treatment prior to the initiation of ICIs treatment affects OS, whereas ATB treatment after the initiation of ICIs treatment affects PFS.

Characteristics of the Intestinal Microbiota in Very Low Birth Weight Infants With Extrauterine Growth Restriction.

Objective: Very low birth weight (VLBW) infants, which experience significant postnatal growth restriction at the time of discharge, are at high risk of later growth failure and long-term consequences. This study aims to characterize the structure of intestinal microbiome community in VLBW infants with extrauterine growth restriction (EUGR). Methods: Twenty-three VLBW infants appropriate for gestational age (GA) hospitalized at the neonatal intensive care unit of the BaoAn Maternal and Child Care Hospital (Shenzhen, China) were enrolled in this study, which were divided into the growth restriction group (EUGR; n = 12) and the normal growth group (AGA; n = 11). Meconium and fecal samples at postnatal day 28 were collected respectively during hospitalization. Total bacterial DNA was extracted and sequenced using the Illumina MiSeq Sequencing System based on the V3-V4 hyper-variable regions of the 16S rRNA gene. Results: The intestinal bacterial communities of preterm infants were dominated by the phylum Proteobacteria. Compared with the AGA group, the relative abundances of the genera Aeromicrobium and Serratia in meconium samples significantly decreased, whereas genera Parabacteroides, Ruminococcus, Blautia, and Aeromonas were more prevalent in the EUGR group. On postnatal day 28, the relative abundances of the genera Parabacteroides, Bacteroides, Eubacterium, Granulicatella, and Salinivibrio were significantly different between the two groups, where genus Salinivibrio decreased significantly in the EUGR samples. Among them, genus Parabacteroides was more abundant on both postnatal day 1 and 28. Further KEGG prediction analysis showed that there were many differences in functional genes and pathways between the two groups on postnatal day 28, but not on day 1, the majority of which were related to energy metabolism. And no statistical differences were observed in the clinical characteristics of infants. Conclusions: Overall, these findings showed that a distinct gut microbiota profile presented in preterm infants with EUGR. The role of intestinal microbiome in the extrauterine growth of preterm infants during hospitalization should be further investigated.

An anti-inflammatory peptide and brain-derived neurotrophic factor-modified hyaluronan-methylcellulose hydrogel promotes nerve regeneration in rats with spinal cord injury.

BACKGROUND: Traumatic spinal cord injury (SCI) causes neuronal death, demyelination, axonal degeneration, inflammation, glial scar formation, and cystic cavitation resulting in interruption of neural signaling and loss of nerve function. Multifactorial targeted therapy is a promising strategy for SCI. METHODS: The anti-inflammatory peptide KAFAKLAARLYRKALARQLGVAA (KAFAK) and brain-derived neurotrophic factor (BDNF)-modified hyaluronan-methylcellulose (HAMC) hydrogel was designed for minimally invasive, localized, and sustained intrathecal protein delivery. The physical and biological characteristics of HAMC-KAFAK/BDNF hydrogel were measured in vitro. SCI model was performed in rats and HAMC-KAFAK/BDNF hydrogel was injected into the injured site of spinal cord. The neuronal regeneration effect was evaluated by inflammatory cytokine levels, behavioral test and histological analysis at 8 weeks post operation. RESULTS: HAMC-KAFAK/BDNF hydrogel showed minimally swelling property and sustained release of the KAFAK and BDNF. HAMC-KAFAK/BDNF hydrogel significantly improved the proliferation of PC12 cells in vitro without cytotoxicity. Significant recovery in both neurological function and nerve tissue morphology in SCI rats were observed in HAMC-KAFAK/BDNF group. HAMC-KAFAK/BDNF group showed significant reduction in proinflammatory cytokines expression and cystic cavitation, decreased glial scar formation, and improved neuronal survival in the rat SCI model compared to HAMC group and SCI group. CONCLUSION: The HAMC-KAFAK/BDNF hydrogel promotes functional recovery of rats with spinal cord injury by regulating inflammatory cytokine levels and improving axonal regeneration.

The Initial Oral Microbiota of Neonates Among Subjects With Gestational Diabetes Mellitus.

Objective: The objective was to investigate the potential effect of gestational diabetes mellitus on the initial neonatal oral microbiome community structure. Methods: Oral samples were collected from 20 full-term, vaginally delivered newborns with sterile swabs. Nine of them had mothers diagnosed with gestational diabetes mellitus (GDM group), while 11 had non-diabetic mothers (NDM group). The oral microbiota was analyzed using multi-barcode 16S rRNA sequencing on Illumina MiSeq system. Results: The results showed that the birth weight, gestational age and gestational weight gain were significantly higher in NDM group. There was a significant correlation between gestational age and birth weight. Neonatal oral microbiome was composed of five dominant phyla from Actinobacteria, Bacteroidetes, Firmicutes, Proteobacteria, and Tenericutes. Compared to NDM group, a higher alpha diversity and reduction of phylum Firmicutes were observed in GDM group. Genus Lactobacillus dominated in NDM group, while Alistipes, Streptococcus, and Faecalibacterium were overabundant in GDM group. Additionally, carbohydrate metabolism increased in NDM group, whereas amino acid metabolism, vitamin metabolism and lipopolysaccharide biosynthesis were more abundant in GDM group. Conclusions: This study showed a distinct oral microbiota profile in neonates born to mothers with GDM, which indicated that maternal diabetes status played an important role in neonatal initial oral microbiota.

miR-1306-3p targets FBXL5 to promote metastasis of hepatocellular carcinoma through suppressing snail degradation.

This study aimed to elucidate the effect of miR-1306-3p on metastasis of hepatocellular carcinoma (HCC) and potential mechanism involved. miR-1306-3p promoted migration and invasion of HCC in vivo and in vitro. Moreover, miR-1306-3p inhibited snail to enhance its expression via directly targeting FBXL5, thus inducing the epithelial-mesenchymal transition (EMT) in HCC. Intriguingly, miR-1306-3p expression was transcriptionally enhanced by FoxM1. Consistently, miR-1306-3p was upregulated in HCC compared with paracarcinoma and correlated with poor prognosis of HCC patients. Our researches suggest that miR-1306-3p is a tumor enhancer in regulating of HCC metastasis, and miR-1306-3p may be clinically utilized as a factor for the clinical diagnosis and prognosis of HCC.

Efficient gene vector with size changeable and nucleus targeting in cancer therapy.

The nucleus is one of the most important cellular organelles, where gene encode and transcribe at that location. However, nucleus-targeting gene delivery are rare been reported. It is important to develop a high-efficiency nucleus-targeting gene vector that can deliver targeted gene into nucleus directly for destroy of cancer cells. Here, special nucleus-targeting and size changeable deliver system based on TAT-SS-PAMAM-D3 with TAT functional on the surface and disulfide linked between D2 and D3 is designed to perform highly efficient nucleus-targeting gene delivery for effective cancer cell killing in vitro. CLSM observations reveal that more TAT-SS-PAMAM-D3 are enter into the nucleus when compare to SS-PAMAM-D3. The TAT modified vector can also act as gene deliver to reach high gene transfection efficiencies, high apoptosis and low viability in HeLa cells. This TAT functionalized and disulfide linking in the carrier may become a prospective vector for cancer gene treatment and also offered a different strategy for designing a better gene delivery system.

A Novel Model for the Entire Settling-Thickening Process in a Secondary Settling Tank.

Sludge settling and thickening occur simultaneously in secondary settling tanks (SSTs). The ability to accurately calculate the settling and thickening capacity of activated sludge was of great importance. Despite extensive studies on the development of settling velocity models for use with SSTs, these models have not been applied due to the difficulty in calibrating the related parameters. Additionally, there have been some studies of the thickening behavior of the activated sludge in SSTs. In this study, a novel settling and thickening model for activated sludge was developed, and the model was validated using experimental data (R2 = 0.830 to 0.963, p < 0.001), which is more reasonable for the characterization of the settling and thickening behavior of the activated sludge in an SST. The application of these models requires only one critical parameter, namely, the stirred sludge volume index SSVI3.5, which is readily available in a water resource recovery facility.

[Influence of Activated Sludge Surface Properties on Flocculating Settling and Effluent Suspend Solid].

In this paper, the influence of the surface properties of the activated sludge on flocculating settling and ESS was studied in seven different sewage treatment plants in Beijing, such as the sludge volume index (SVI), the protein/carbohydrate (P/C) ratio in extracellular polymeric substance, Zeta potential, two-dimensional fractal dimension(D2f). The relationships between the surface properties of the activated sludge and flocculation ability (FA) or effluent suspend solid(ESS) were also analyzed. The results showed that no obvious correlation was obtained between SVI and FA or ESS, but obvious negative correlation between the FA and ESS (R2=0.787) was observed. When the P/C increased from 1.28 to 25.34, the FA could increase from 0.19 to 0.73 correspondingly, but the ESS decreased from 14.89 mg·L-1 to 6.08 mg·L-1. This was because the amino acids in protein with positive charge could neutralize the negative charge on the surface of floc, the increase of protein ratio in EPS could decrease the absolute value of Zeta potential, which made a contribution to form more stable floc structure, and improved the ability of flocculation. Moreover, the Zeta potential had a positive correlation with FA but a negative correlation with ESS. The absolute value of Zeta potential decreased by 1 mV, FA increased by 0.059 and ESS decreased by 0.934 mg·L-1 correspondingly. In addition, there was an obvious index correlation (R2=0.935, P<0.01) between D2f and FA; While D2f increased from 1.10 to 1.45, FA could increase by 4.3 times and ESS decreased linearly (R2=0.868).

Modeling the Activated Sludge--Thickening Process in Secondary Settlers.

A single paragraph of about 200 words maximum. For research articles; abstracts should give a pertinent overview of the work. We strongly encourage authors to use the following style of structured abstracts; but without headings: (1) BACKGROUND: Place the question addressed in a broad context and highlight the purpose of the study; (2) METHODS: Describe briefly the main methods or treatments applied; (3) RESULTS: Summarize the article's main findings; and (4) CONCLUSION: Indicate the main conclusions or interpretations. The abstract should be an objective representation of the article: it must not contain results which are not presented and substantiated in the main text and should not exaggerate the main conclusions.

[Establishment of animal model of myoclonus originating from axis of cortex-thalamus].

OBJECTIVE: To develop a series of experimental animal models of myoclonus with different origins consistent with myoclonus seizure in clinic setting. METHODS: GABA(A) antagonist SR95531 was microinjected into the primary motor cortex (PMC), corpus striatum, nucleus reticular of the thalamus (NRT) to induce myoclonus (EMG burst of myoclonus