Interleukin-41: a novel serum marker for the diagnosis of alpha-fetoprotein-negative hepatocellular carcinoma.

Background: For the lack of effective serum markers for hepatocellular carcinoma(HCC) diagnosis, it is difficult to detect liver cancer and identify its recurrence early. Methods: Databases were used to analyze the genes potentially associated with alpha-fetoprotein(AFP). ELISA assay was used to detect the serum IL-41 in HCC, liver metastases, hepatitis, and healthy people. Immunohistochemical staining was used to analyze the relative quantification of IL-41 in HCC and paracancer tissues. Various survival curves were plotted according to clinical pathological data and helped us draw the ROC curve of IL-41 diagnosis of HCC. Results: The serum expression of IL-41 was highest in AFP negative HCC patients and significantly higher than that in AFP positive HCC and metastatic cancer patients. There was a significant negative correlation between elevated serum IL-41 and AFP(<1500ng/ml). The clinicopathological features suggested that the serum IL-41 level was significantly correlated with capsule invasion, low differentiation and AFP. High serum expression of IL-41 suggests poorer survival and earlier recurrence after resection, and IL-41 upregulated in patients with early recurrence and death. The expression of IL-41 was higher in HCC tissues of patients with multiple tumors or microvascular invasion. The ROC curve showed that serum IL-41 had a sensitivity of 90.17 for HCC and a sensitivity of 96.63 for AFP-negative HCC, while the specificity was higher than 61%. Conclusion: IL-41 in serum and tissue suggests poor prognosis and postoperative recurrence in HCC patients and could be a new serum diagnostic marker for AFP negative patients.

Exosomal miR-19a decreases insulin production by targeting Neurod1 in pancreatic cancer associated diabetes.

BACKGROUND: New onset diabetes mellitus demonstrates a roughly correlation with pancreatic cancer (PaC), which is unique in PaC and was named as PaC-induced DM, but the inner mechanism remains unclear. Exosomes mediate intercellular communication and bearing microRNAs might be direct constituent of effect in target cells. METHODS AND RESULTS: The isolated exosomes from PaC cells were used to treat pancreatic ß cells or the primary mice islets, and the glucose stimulated insulin secretions were measured. We validated the exosomal miR-19a from PaC cells to be an important mediator in the down regulation of insulin secretion by targeting Neurod1, the validated gene involved in insulin secretion, by using the quantitative real-time PCR, western blot, and promoter luciferase activity. The relative insulin, cAMP and Ca2+ expressions were also assayed to verify the inverse correlation between cancerous miR-19a and pancreatic islets Neurod1. CONCLUSIONS: Our study indicated that signal changes between cancer cells and ß cells via exosomes might be important in the pathogenesis of PaC-induced DM and supplemented the pathogenesis of PaC-induced DM and provide a possible access of PaC screening strategy.

Smoothing Complete Feature Pyramid Networks for Roll Mark Detection of Steel Strips.

Steel strip acts as a fundamental material for the steel industry. Surface defects threaten the steel quality and cause substantial economic and reputation losses. Roll marks, always occurring periodically in a large area, are put on the top of the list of the most serious defects by steel mills. Essentially, the online roll mark detection is a tiny target inspection task in high-resolution images captured under harsh environment. In this paper, a novel method-namely, Smoothing Complete Feature Pyramid Networks (SCFPN)-is proposed for the above focused task. In particular, the concept of complete intersection over union (CIoU) is applied in feature pyramid networks to obtain faster fitting speed and higher prediction accuracy by suppressing the vanishing gradient in training process. Furthermore, label smoothing is employed to promote the generalization ability of model. In view of lack of public surface image database of steel strips, a raw defect database of hot-rolled steel strip surface, CSU_STEEL, is opened for the first time. Experiments on two public databases (DeepPCB and NEU) and one fresh texture database (CSU_STEEL) indicate that our SCFPN yields more competitive results than several prestigious networks-including Faster R-CNN, SSD, YOLOv3, YOLOv4, FPN, DIN, DDN, and CFPN.

Near-Infrared-Induced Contractile Proteinosome Microreactor with a Fast Control on Enzymatic Reactions.

Inspired by the compartmentalized structure of cells, self-regulating responsive hollow microcapsules are highly desirable for the modulation of enzymatic reactions. Here, we report a strategy to fabricate gold nanorod embedded proteinosomes by covalently grafting gold nanorods onto the surface of proteinosomes. The excellent photothermal conversion efficiency of the embedded gold nanorod and the thermal phase transition of the grafted PNIPAAm allow the constructed hybrid proteinosomes to show reversible contraction behaviors triggered by near-infrared light with the molecular weight cutoff of the membrane decreased to ca. 50 kDa, and importantly, the contraction frequency of the constructed proteinosomes could be as fast as 1 min and last for at least 15 cycles. Subsequently, the effective encapsulation of three cascade enzymes into the proteinosomes realizes the construction of a near-infrared responsive microreactor that allows control of the cascade reaction by near-infrared illumination, thereby enabling reversible on and off of the enzymatic reaction. Such microcapsule-based reactors demonstrate the potential to alter the membrane molecular weight cutoff, and it is believed that the development of such responsive microcapsules will have great potential for studying cellular responses and provide a platform for future applications in biosensing and drug delivery.

Facile Synthesis of Super-Microporous Titania-Alumina with Tailored Framework Properties.

Super-microporous material (pore size 1-2 nm) can bridge the pore size gap between the zeolites (<1 nm) and the mesoporous oxides (>2 nm). A series of super-microporous titania-alumina materials has been successfully prepared via a facile one-pot evaporation-induced self-assembly (EISA) strategy by different solvents using fatty alcohol polyoxyethylene ether (AEO-7) as the template. Moreover, no extra acid or base is added in our synthesis process. When titanium isopropylate is used as the titanium source, these materials exhibit high BET surface areas (from 275 to 396 m2/g) and pore volumes (from 0.14 to 0.18 cm3/g). The sample prepared using methanol as the solvent shows the largest Brunauer-Emmett-Teller (BET) surface area of 396 m2/g. When tetrabutyl titanate is used as the titanium source, these materials exhibit high BET surface areas (from 282 to 396 m2/g) and pore volumes (from 0.13 to 0.18 cm3/g). The sample prepared using ethanol as the solvent shows the largest BET surface area of 396 m2/g.

Interfacial self-assembly of gold nanoparticle-polymer nanoconjugates into microcapsules with near-infrared light modulated biphasic catalysis efficiency.

A high throughput way to generate gold nanoparticle-based microcapsules was demonstrated based on the interfacial assembly in a water and 2-ethyl-1-hexanol two phase system. The obtained gold microcapsules exhibit superior stability, good flexibility, ductility, and a significant enhancement (about 10-fold) in the biphasic catalytic reaction rate upon near-infrared light irradiation.

Integrative Analysis of MicroRNAome, Transcriptome, and Proteome during the Limb Regeneration of Cynops orientalis.

Salamanders completely regenerate their limbs after amputation. Thus, these animals are unique models to investigate the mechanisms modulating regeneration in vertebrates. To investigate the influence of microRNAs (miRNAs) on newt limb regeneration, the miRNAs and mRNAs were simultaneously profiled using Illumina HiSeq 2500 System during limb regeneration of Cynops orientalis at 3, 7, 14, 30 and 42 days postamputation. A total of 203 miRNAs and 4230 mRNAs were identified to be differentially expressed. Together with the proteomic data obtained from our previous study, integrative analysis of multiple profiling data sets was performed to construct an interaction network of differentially expressed miRNAs, mRNAs and proteins. Results of GO and KEGG analyses showed that the differentially expressed miRNA targets were mainly directed to cytoskeletal remodeling and carbohydrate metabolism. The stage-specific regulation of miRNAs on their targets was analyzed by hierarchical clustering analysis and validated by qRT-PCR. The negative regulation of miR-223 and miR-133a on their targets was tested by performing dual luciferase reporter assay. The integration analysis will provide a powerful tool to identify the regulatory mechanisms of miRNAs and their targets. The results may have implications in understanding the complex mechanisms underlying newt limb regeneration.

Signal-On Electrochemiluminescence of Self-Ordered Molybdenum Oxynitride Nanotube Arrays for Label-Free Cytosensing.

In this paper, a signal-on electrochemiluminescence (ECL) cytosensing platform was developed based on nitrogen doped molybdenum oxynitride nanotube arrays (MoO xN y NTs) for the first time. The MoO xN y NTs exhibited excellent cathodic ECL behavior with 2-(dibutylamino)-ethanol (DBAE) as a coreactant. Owing to the surface plasmon resonance (SPR) of Au triggered by the ECL emission, the generation of "hot electrons" on AuNPs hampered DBAE to give off electrons and leads to the ECL quenching. This process could be hindered via adding "barriers" on the surface of AuNPs, such as antibody molecules and cells, to achieve the signal recovery. Based on the quenching-recovering mechanism, a facile label-free ECL cytosensor was constructed. The linear response of HepG2 cells was in the range of 50-13800 cells mL-1 with a low detection limit of 47 cells mL-1 (S/N = 3). Moreover, the proposed ECL cytosensor exhibits a satisfying performance in the practical application. Due to the anodic formation from a Mo metal substrate, the valuable feature is that the MoO xN y NTs-based ECL cytosensor can be used directly, thereby providing a stable and simplified ECL cytosensing platform for future clinical applications.

MicroRNA-148a Suppresses the Proliferation and Migration of Pancreatic Cancer Cells by Down-regulating ErbB3.

OBJECTIVES: ErbB3 (HER3) has been associated with pancreatic cancer progression, but little is known about its regulatory mechanisms. We investigated whether microRNAs (miRNAs) regulate levels of ErbB3 in pancreatic cancer cells. METHODS: We used bioinformatic analyses to search for miRNAs that can potentially target ERBB3. Furthermore, the biological consequences of the targeting of ERBB3 by miR-148a were examined by cell proliferation and migration assays in vitro. RESULTS: We identified an inverse correlation between miR-148a and ErbB3 protein levels in pancreatic cancer tissue samples and cell lines. We identified that miR-148a directly recognizes the 3'-UTR of the ErbB3 transcript and regulates ErbB3 expression. We demonstrated that the repression of ERBB3 by miR-148a suppressed the proliferation and migration of pancreatic cancer cells. In PANC-1 pancreatic cancer cells, the repression of ErbB3 by miR-148a inhibited the phosphorylation of ERK1/2 and AKT, which eventually repressed the proliferation and migration of these cells. CONCLUSIONS: Taken together, the present study provides the first evidence that miR-148a plays a significant role in the suppression of pancreatic tumorigenesis via the inhibition of ErbB3 translation.

Brachybacterium hainanense sp. nov., isolated from noni (Morinda citrifolia L.) branch.

A Gram-stain-positive bacterial strain, designated as NR2T, isolated from noni (Morinda citrifolia L.) branch was investigated using a polyphasic taxonomic approach. The cells were small coccoid to ovoid, non-spore-forming and motile. Phylogenetic analysis based on 16S rRNA gene sequences showed that the strain was a representative of a member of the genus Brachybacterium, to which the most closely related neighbours were Brachybacterium squillarum M-6-3T (97.90 % similarity), Brachybacterium faecium DSM 4810T (97.50 %), Brachybacterium sacelli LMG 20345T (97.41 %), Brachybacterium phenoliresistens phenol-AT (97.36 %), Brachybacterium nesterenkovii DSM 9573T (97.36 %) and Brachybacterium rhamnosum LMG 19848T (97.32 %). The polar lipid profile of strain NR2T consisted of diphosphatidylglycerol, phosphatidylglycerol, unknown phospholipids and unknown glycolipids. The predominant respiratory quinone was MK-8, with MK-9 and MK-7 as minor components. The major fatty acids were anteiso-C15 : 0 and iso-C15 : 0. Strain NR2T was clearly distinguishable from the type strains of related species on the basis of phylogenetic analysis, DNA-DNA hybridization, fatty acid composition data analysis and a range of physiological and comparison of biochemical characteristics. It is evident from the genotypic and phenotypic data that strain NR2T represents a novel species of the genus Brachybacterium, for which the name Brachybacterium hainanense sp. nov. is proposed. The type strain is NR2T ( = DSM 29535T = CICC 10874T).

Pancreatic cancer-secreted miR-155 implicates in the conversion from normal fibroblasts to cancer-associated fibroblasts.

Cancer-associated fibroblasts (CAF) are a major constituent of the pancreatic cancer microenvironment and that the meaning is as intended. Pancreatic cancer cells can induce normal fibroblasts to convert into CAF and, reciprocally, CAF promote tumor invasions and proliferations. The mechanism of the conversion from normal fibroblasts (NF) to CAF remains unclear. MicroRNA are short non-coding RNA involved in the post-transcription gene regulation, which have been defined as an imperative controller in tumor invasions, proliferations and colony formations. Microvesicles (MV) have been proved to be an important mediator of intercellular communication and can selectively transport secreted microRNA from a donor cell into a recipient cell. In this study, we isolated primary pancreatic fibroblasts from wild type C57 mice and co-cultured them with pancreatic cancer cell lines, BxPC-3 and SW1990, and observed the conversion from NF to CAF, or at least CAF-like cells. This phenomenon could also be replicated in primary fibroblasts treated with MV separated from a cancer cell media. We identified that miR-155 was upregulated in PaC-derived MV and we confirmed that normal fibroblasts could convert into CAF after MV containing miR-155 had been taken up. TP53INP1 is a target of miR-155 in fibroblasts and a downregulation of TP53INP1 protein levels could contribute to the fibroblasts' activation. These results indicated that pancreatic cancer cells might reprogram normal adjacent fibroblasts into CAF by means of secreted MV containing miR-155. Targeting the circulating microRNA might be a potential therapy for malignant tumors.

Sphingomonas morindae sp. nov., isolated from Noni (Morinda citrifolia L.) branch.

Two yellow bacterial strains, designated NBD5(T) and NBD8, isolated from Noni (Morinda citrifolia L.) branch were investigated using a polyphasic taxonomic approach. Cells were Gram-stain-negative, aerobic, non-spore-forming, non-motile and short rod-shaped. Phylogenetic analysis based on 16S rRNA gene sequences suggested that the strains were members of a novel species of the genus Sphingomonas, the seven closest neighbours being Sphingomonas oligoaromativorans SY-6(T) (96.9% similarity), Sphingomonas polyaromaticivorans B2-7(T) (95.8%), Sphingomonas yantingensis 1007(T) (94.9%), Sphingomonas sanguinis IFO 13937(T) (94.7%), Sphingomonas ginsenosidimutans Gsoil 1429(T) (94.6%), Sphingomonas wittichii RW1(T) (94.6%) and Sphingomonas formosensis CC-Nfb-2(T) (94.5%). Strains NBD5T and NBD8 had sphingoglycolipid, phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylglycerol and phosphatidylcholine as the major polar lipids, ubiquinone 10 as the predominant respiratory quinone, and sym-homospermidine as the major polyamine. Strains NBD5(T) and NBD8 were clearly distinguished from reference type strains based on phylogenetic analysis, DNA-DNA hybridization, fatty acid composition data analysis, and comparison of a range of physiological and biochemical characteristics. It is evident from the genotypic and phenotypic data that strains NBD5(T) and NBD8 represent a novel species of the genus Sphingomonas, for which the name Sphingomonas morindae sp. nov. is proposed. The type strain is NBD5(T) ( = DSM 29151(T) = KCTC 42183(T) = CICC 10879(T)).

MiR-143 and MiR-145 regulate IGF1R to suppress cell proliferation in colorectal cancer.

Insulin-like growth factor 1 receptor (IGF1R) is a transmembrane receptor that is activated by insulin-like growth factor 1 (IGF-1) and by a related hormone called IGF-2. It belongs to the large class of tyrosine kinase receptors and plays an important role in colorectal cancer etiology and progression. In this study, we used bioinformatic analyses to search for miRNAs that potentially target IGF1R. We identified specific target sites for miR-143 and miR-145 (miR-143/145) in the 3'-untranslated region (3'-UTR) of the IGF1R gene. These miRNAs are members of a cluster of miRNAs that have been reported to exhibit tumor suppressor activity. Consistent with the bioinformatic analyses, we identified an inverse correlation between miR-143/145 levels and IGF1R protein levels in colorectal cancer tissues. By overexpressing miR-143/145 in Caco2, HT29 and SW480 colorectal cancer cells, we experimentally validated that miR-143/145 directly recognizes the 3'-UTR of the IGF1R transcript and regulates IGF1R expression. Furthermore, the biological consequences of the targeting of IGF1R by miR-143/145 were examined by cell proliferation assays in vitro. We demonstrated that the repression of IGF1R by miR-143/145 suppressed the proliferation of Caco2 cells. Taken together, our findings provide evidence for a role of the miR-143/145 cluster as a tumor suppressor in colorectal cancer through the inhibition of IGF1R translation.