Single-cell transcriptome analyses reveal signals to activate dormant neural stem cells.

The scarcity of tissue-specific stem cells and the complexity of their surrounding environment have made molecular characterization of these cells particularly challenging. Through single-cell transcriptome and weighted gene co-expression network analysis (WGCNA), we uncovered molecular properties of CD133(+)/GFAP(-) ependymal (E) cells in the adult mouse forebrain neurogenic zone. Surprisingly, prominent hub genes of the gene network unique to ependymal CD133(+)/GFAP(-) quiescent cells were enriched for immune-responsive genes, as well as genes encoding receptors for angiogenic factors. Administration of vascular endothelial growth factor (VEGF) activated CD133(+) ependymal neural stem cells (NSCs), lining not only the lateral but also the fourth ventricles and, together with basic fibroblast growth factor (bFGF), elicited subsequent neural lineage differentiation and migration. This study revealed the existence of dormant ependymal NSCs throughout the ventricular surface of the CNS, as well as signals abundant after injury for their activation.

Propionate promotes vitamin D receptor expression via yes-associated protein in rats with short bowel syndrome.

Vitamin D deficiency and refractory osteoporosis are common complications in patients with short bowel syndrome (SBS). The symptom of bone loss is not effectively alleviated, even after the oral administration of vitamin D in SBS patients who had been weaned off parenteral nutrition. In this study, we aimed to investigate the effect of propionate on the expression of the vitamin D receptor (VDR) in the small intestine of rats with SBS. Firstly, IEC-6 (intestinal epithelioid cell line No. 6) cells were incubated in vitro with 1 mM sodium propionate for 24 h. This resulted in a significant increase in the expression of VDR and yes-associated protein (YAP) compared with that in the control group. Transfection of IEC-6 cells with YAP siRNA significantly down-regulated the expression of VDR. By contrast, after incubating IEC-6 cells with lysophosphatidic acid, an agonist of YAP, upregulation of VDR and YAP was observed. Next, we investigated whether this effect occurs in vivo. Five-week-old male Sprague-Dawley rats underwent 80% small bowel resection to establish an SBS model. Rats treated with 1% w/v sodium propionate had high levels of VDR and YAP expression in the intestine and intestinal adaptation was clearly observed compared to the control group. However, these effects were blocked by intraperitoneal injection of verteporfin. Thus, this study showed that propionate promoted VDR expression in the intestine via the activity of YAP, both in vitro and in vivo. Moreover, propionate was shown to play an active role in postoperative intestinal adaptation in SBS rats.

Anisotropic infrared plasmonic broadband absorber based on graphene-black phosphorus multilayers.

Two-dimensional materials (2DMs) such as graphene and black phosphorus (BP) have aroused considerable attentions in the past few years. Engineering and enhancing their light-matter interaction is possible due to their support for localized surface plasmon resonances in the infrared regime. In this paper, we have proposed an infrared broadband absorber consisting of multilayer graphene-BP nanoparticles sandwiched between dielectric layers. Benefiting from the properties of graphene and BP, the absorber exhibits both perfect broadband responses and strong anisotropy beyond individual graphene and BP layers. The absorber is tunable with the variation of geometric parameters as well as the doping levels of graphene and BP. The physical insight is revealed by electric field distributions. Furthermore, the angular robustness for incident wave is investigated. The proposed anisotropic omnidirectional broadband absorber may have promising potential applications in various biosensing, communication and imaging systems.

Rotating Machinery Fault Diagnosis Based on Improved Multiscale Amplitude-Aware Permutation Entropy and Multiclass Relevance Vector Machine.

The health state of rotating machinery directly affects the overall performance of the mechanical system. The monitoring of the operation condition is very important to reduce the downtime and improve the production efficiency. This paper presents a novel rotating machinery fault diagnosis method based on the improved multiscale amplitude-aware permutation entropy (IMAAPE) and the multiclass relevance vector machine (mRVM) to provide the necessary information for maintenance decisions. Once the fault occurs, the vibration amplitude and frequency of rotating machinery obviously changes and therefore, the vibration signal contains a considerable amount of fault information. In order to effectively extract the fault features from the vibration signals, the intrinsic time-scale decomposition (ITD) was used to highlight the fault characteristics of the vibration signal by extracting the optimum proper rotation (PR) component. Subsequently, the IMAAPE was utilized to realize the fault feature extraction from the PR component. In the IMAAPE algorithm, the coarse-graining procedures in the multi-scale analysis were improved and the stability of fault feature extraction was promoted. The coarse-grained time series of vibration signals at different time scales were firstly obtained, and the sensitivity of the amplitude-aware permutation entropy (AAPE) to signal amplitude and frequency was adopted to realize the fault feature extraction of coarse-grained time series. The multi-classifier based on the mRVM was established by the fault feature set to identify the fault type and analyze the fault severity of rotating machinery. In order to demonstrate the effectiveness and feasibility of the proposed method, the experimental datasets of the rolling bearing and gearbox were used to verify the proposed fault diagnosis method respectively. The experimental results show that the proposed method can be applied to the fault type identification and the fault severity analysis of rotating machinery with high accuracy.

High-Throughput Data of Circular RNA Profiles in Human Temporal Cortex Tissue Reveals Novel Insights into Temporal Lobe Epilepsy.

BACKGROUND/AIMS: Circular RNAs (circRNAs) are a class of long noncoding RNAs with a closed loop structure that regulate gene expression as microRNA sponges. CircRNAs are more enriched in brain tissue, but knowledge of the role of circRNAs in temporal lobe epilepsy (TLE) has remained limited. This study is the first to identify the global expression profiles and characteristics of circRNAs in human temporal cortex tissue from TLE patients. METHODS: Temporal cortices were collected from 17 TLE patients and 17 non-TLE patients. Total RNA was isolated, and high-throughput sequencing was used to profile the transcriptome of dysregulated circRNAs. Quantitative PCR was performed for the validation of changed circRNAs. RESULTS: In total, 78983 circRNAs, including 15.29% known and 84.71% novel circRNAs, were detected in this study. Intriguingly, 442 circRNAs were differentially expressed between the TLE and non-TLE groups (fold change≥2.0 and FDR≤0.05). Of these circRNAs, 188 were up-regulated, and 254 were down-regulated in the TLE patient group. Eight circRNAs were validated by real-time PCR. Remarkably, circ-EFCAB2 was intensely up-regulated, while circ-DROSHA expression was significantly lower in the TLE group than in the non-TLE group (P<0.05). Bioinformatic analysis revealed that circ-EFCAB2 binds to miR-485-5p to increase the expression level of the ion channel CLCN6, while circ-DROSHA interacts with miR-1252-5p to decrease the expression level of ATP1A2. CONCLUSIONS: The dysregulations of circRNAs may reflect the pathogenesis of TLE and circ-EFCAB2 and circ-DROSHA might be potential therapeutic targets and biomarkers in TLE patients.

Optimization of lithography source illumination arrays using diffraction subspaces.

An efficient and robust lithography illumination optimization (ILO) approach is developed based on subspace compressive sensing (CS) and an lp-norm reconstruction algorithm. Instead of optimizing the source pattern over all its degrees of freedom, the proposed method only optimizes the source pixels in a subspace. The subspace includes the source pixels inducing interference between different diffraction orders of the mask pattern. The ILO is then formulated as an lp-norm (0 < p < 1) inverse reconstruction problem under the sparse representation of the source pattern. The subspace CS method benefits from having a significantly smaller number of optimization variables, thus effectively improving the computation speed. In addition, an lp-norm reconstruction algorithm is used, which is more robust than l1-norm reconstruction algorithms. Based on the simulations at 45nm and 14nm technology nodes, the proposed methods prove to improve the computational efficiency, robustness and imaging performance of current ILO methods based on adaptive CS.

(R)-panaxadiol by whole cells of filamentous fungus Absidia coerulea AS 3.3382.

The microbial transformation of 20(R)-panaxadiol (PD) by the fungus Absidia coerulea AS 3.3382 afforded three new and three known metabolites. The structures of the metabolites were characterized as 3-oxo-20(R)-panaxadiol (1), 3-oxo-7ß- hydroxyl-20(R)-panaxadiol (2), 3-oxo-22ß-hydroxyl-20(R)-panaxadiol (3), 3-oxo- 7ß,22ß-dihydroxyl-20(R)-panaxadiol (4), 3-oxo-7ß,24ß-dihydroxyl-20(R)-panaxadiol (5), and 3-oxo-7ß,24α-dihydroxyl-20(R)-panaxadiol (6). Among them, 2-4 were new compounds. In addition, compounds 3 and 4 exhibited significant anti-hepatic fibrosis activity.

Fast lithographic source optimization using a batch-processing sequential least square estimator.

This paper proposes a fast source optimization (SO) method for lithography systems to improve the imaging performance of different hotspots on the fullchip layout. Hotspots are referred to as the critical locations on the layout that are difficult to print. A fullchip layout usually includes numerous hotspots with different geometric characteristics. Current SO approaches collect all of the data from different hotspots before the optimization, and then try to calculate the common optimal source for all hotspots. If any new data from unaccounted hotspots become available, the optimal source has to be recalculated. This paper first develops a batch-processing sequential least square estimator, and then uses it to iteratively modify the source pattern based on the ongoing hotspot data. The optimized source for one hotspot can be updated to suit others without redundant computation. Simulations show that the proposed method can significantly accelerate the SO procedure, while improving the imaging performance of multiple hotspots.

Quantitative assessment of parkinsonian bradykinesia based on an inertial measurement unit.

BACKGROUND: As the most characteristic feature of Parkinson's disease (PD), bradykinesia (slowness of movement) affects all patients with Parkinson's disease and interferes with their daily activities. This study introduces a wearable bradykinesia assessment system whose core component is composed of an inertial measurement unit. METHODS: The system diagram and assessment task were defined in accordance with clinical requirements from neurologists. Based on hand grasping actions, calculations of hand grasping ranges and statistical methods of quantitatively assessing parkinsonian bradykinesia were presented. Seven control subjects and eight patients were tested with this system. RESULTS: Experimental results show that a calculated bradykinesia parameter (modified mean range, instead of mean and standard deviation of the grasp ranges) correlated well with the evaluations of a neurologist (Pearson's correlation coefficient r = -0.83, p < 0.001). CONCLUSIONS: The bradykinesia assessment system was tested on both health subjects and PD patients. The results show that this system has greater correlation with the evaluations by neurologists than other parkinsonian bradykinesia assessment systems. The modified mean range was verified as the major bradykinesia parameter (key indicator). This study is helpful to those who want to use consumer-grade inertial sensors for quantitative assessment of motor symptoms during treatment.

[Mahalanobis distance based hyperspectral characteristic discrimination of leaves of different desert tree species].

The hyperspectral reflectance of Populus euphratica, Tamarix hispida, Haloxylon ammodendron and Calligonum mongolicum in the lower reaches of Tarim River and Turpan Desert Botanical Garden was measured by using the HR-768 field-portable spectroradiometer. The method of continuum removal, first derivative reflectance and second derivative reflectance were used to deal with the original spectral data of four tree species. The method of Mahalanobis Distance was used to select the bands with significant differences in the original spectral data and transform spectral data to identify the different tree species. The progressive discrimination analyses were used to test the selective bands used to identify different tree species. The results showed that The Mahalanobis Distance method was an effective method in feature band extraction. The bands for identifying different tree species were most near-infrared bands. The recognition accuracy of four methods was 85%, 93.8%, 92.4% and 95.5% respectively. Spectrum transform could improve the recognition accuracy. The recognition accuracy of different research objects and different spectrum transform methods were different. The research provided evidence for desert tree species classification, monitoring biodiversity and the analysis of area in desert by using large scale remote sensing method.

Platelet-rich plasma injection for enterocutaneous fistula: a case report.

INTRODUCTION: An ECF is an abnormal communication between the small or large bowel and the skin. PRP provides a variety of bioactive factors to promote wound healing. This case report details the use of PRP in the management of ECF. CASE REPORT: A 52-year-old male with a history of duodenal perforation and duodenal fistula repair surgery presented with intermittent discharge of light-yellow material from the drainage tube removal site. Symptoms had not improved after 7 months of dressing changes. The patient had no signs or symptoms of generalized sepsis or peritonitis. A diagnosis of ECF was made based on the symptoms and physical examination. One application of PRP was injected into the fistula, and the fistula closed within 2 weeks. At 6-month follow-up, the patient had neither fistula recurrence nor abdominal pain. CONCLUSIONS: The findings in this case report suggest that PRP can be used in the management of ECF in patients with no signs and symptoms of generalized sepsis or peritonitis to promote fistula closure and decrease time to healing.

Genome-wide DNA methylation analysis of cognitive function in middle and old-aged Chinese monozygotic twins.

Cognitive ability plays an important role in mental and physical well-beings in the increasingly ageing populations. Here, based on a sample of 30 cognitive function-discordant monozygotic twin pairs, we aimed to detect specific epigenetic variants potentially related to cognitive function by conducting an epigenome-wide association study (EWAS). Association between methylation level of single CpG site with cognitive function score was tested by linear mixed effect model. Functions of cis-regulatory regions and ontology enrichments were predicted by Genomic Regions Enrichment of Annotations Tool (GREAT). Differentially methylated regions (DMRs) were detected by comb-p python library. A list of 28 CpG sites were identified to reach the level of P < 1 × 10-4, and the strongest association (cor = 0.138, P = 2.549 × 10-6) was detected for DNA CpG site (Chr17: 40,700,490 bp) located at HSD17B1P1. The identified 14,065 genomic CpG sites (P < 0.05) were mapped to 2646 genes, especially HSD17B1P1, CUL4A, INTS8, GFI1B, ZNF467, CDH15, and PSMA1. GREAT ontology enrichments mainly highlighted nicotine pharmacodynamics pathway, GABA-B receptor II/nicotinic acetylcholine receptor/hedgehog/endothelin/Wnt signaling pathways, Parkinson disease, Huntington disease, glycolysis, neuronal system, and toll-like receptor binding. We detected 15 DMRs located at/near 16 genes, especially LINC01551, LINC02282, and FAM32A. And 32 cognitive function-associated differentially methylated genes could be replicated, such as SHANK2, ABCA2, PRDM16, NCOR2, and INPP5A. Our EWAS in monozygotic twins identify specific epigenetic variations which are significantly involved in functional genes, biological function and pathways that mediate cognitive function. The findings provide clues to further identify new diagnostic biomarkers and therapeutic targets for cognitive dysfunction.

Microbial hydroxylation and glycosidation of oleanolic acid by Circinella muscae and their anti-inflammatory activities.

Biotransformation of oleanolic acid (OA) by Circinella muscae AS 3.2695 was investigated. Nine hydroxylated and glycosylated metabolites (1-9) were obtained. Their structures were elucidated as 3ß,7ß-dihydroxyolean-12-en-28-oic acid (1), 3ß,7ß,21ß-trihydroxyolean-12-en-28-oic acid (2), 3ß,7α,21ß-trihydroxyolean-12-en- 28-oic acid (3), 3ß,7ß,15α-trihydroxyolean-12-en-28-oic acid (4), 7ß,15α-dihydroxy- 3-oxo-olean-12-en-28-oic acid (5), 7ß-hydroxy-3-oxo-olean-12-en-28-oic acid (6), oleanolic acid-28-O-ß-D-glucopyranosyl ester (7), 3ß,21ß-dihydroxyolean-12-en-28- oic acid-28-O-ß-D-glucopyranosyl ester (8), and 3ß,7ß,15α-trihydroxyolean-12-en- 28-oic acid-28-O-ß-D-glucopyranosyl ester (9) by spectroscopic analysis. Among them, compounds 4 and 9 were new compounds. In addition, anti-inflammatory activities were assayed and evaluated for the isolated metabolites. Most of the metabolites exhibited significant inhibitory activities on lipopolysaccharides-induced NO production in RAW 264.7 cells.

Microbial transformation of the anti-aging agent cycloastragenol by Mucor racemosus.

The microbial transformation of cycloastragenol (CA) by Mucor racemosus AS 3.20 was investigated. Seven isolated products were identified as (20R,24S)-3ß,6α,16ß,25- tetrahydroxy-20,24-epoxy-9,10-seco-cycloartan-9(11),10(19)-diene (1), (20R,24S)- 3ß,6α,16ß,25-tetrahydroxy-20,24-epoxy-9,10-seco-cycloartan-1(10),9(11)-diene (2), (20R,24S)-3ß,16ß,25-trihydroxy-6α,19α;20,24-diepoxy-9,10-seco-cycloartan-9(11)-ene (3), (20R,24S)-6α,16ß,25-trihydroxy-3ß,10ß;20,24-diepoxy-9,10-seco- cycloartan-11-one (4), (20R,24S)-16ß,25-dihydroxy-6α-methoxy-3ß,10ß;20,24- diepoxy-9,10-seco-cycloartan-7(8),9(11)-diene (5), (20R,24S)-6α,16ß,25-trihydroxy-3ß,10ß;20,24-diepoxy-9,10-seco-cycloartan-9(11)-ene (6), and (20R,24S)-3ß,6α,16ß,25-tetrahydroxy-19-acetoxy-ranunculan-9(10)-ene (7) by spectroscopic analysis. Among them, compounds 2 and 5 were new compounds. M. racemosus could catalyze ring expansion and epoxidation reactions to form 3ß,10ß-epoxy- or 6α,19α-epoxy-9,10-seco-cycloartane structures. These regio- and stereo-selective reactions are difficult to achieve by chemical means. In addition, the biological effects of isolated metabolites on increasing the lifespan of Caenorhabditis elegans were evaluated. Most of the metabolites could significantly extend the lifespan of C. elegans at 50 µM.

Long noncoding RNA CCDC144NL-AS1 knockdown induces naïve-like state conversion of human pluripotent stem cells.

BACKGROUND: Human naïve pluripotency state cells can be derived from direct isolation of inner cell mass or primed-to-naïve resetting of human embryonic stem cells (hESCs) through different combinations of transcription factors, small molecular inhibitors, and growth factors. Long noncoding RNAs (lncRNAs) have been identified to be crucial in diverse biological processes, including pluripotency regulatory circuit of mouse pluripotent stem cells (PSCs), but few are involved in human PSCs' regulation of pluripotency and naïve pluripotency derivation. This study initially planned to discover more lncRNAs possibly playing significant roles in the regulation of human PSCs' pluripotency, but accidently identified a lncRNA whose knockdown in human PSCs induced naïve-like pluripotency conversion. METHODS: Candidate lncRNAs tightly correlated with human pluripotency were screened from 55 RNA-seq data containing human ESC, human induced pluripotent stem cell (iPSC), and somatic tissue samples. Then loss-of-function experiments in human PSCs were performed to investigate the function of these candidate lncRNAs. The naïve-like pluripotency conversion caused by CCDC144NL-AS1 knockdown (KD) was characterized by quantitative real-time PCR, immunofluorescence staining, western blotting, differentiation of hESCs in vitro and in vivo, RNA-seq, and chromatin immunoprecipitation. Finally, the signaling pathways in CCDC144NL-AS1-KD human PSCs were examined through western blotting and analysis of RNA-seq data. RESULTS: The results indicated that knockdown of CCDC144NL-AS1 induces naïve-like state conversion of human PSCs in the absence of additional transcription factors or small molecular inhibitors. CCDC144NL-AS1-KD human PSCs reveal naïve-like pluripotency features, such as elevated expression of naïve pluripotency-associated genes, increased developmental capacity, analogous transcriptional profiles to human naïve PSCs, and global reduction of repressive chromatin modification marks. Furthermore, CCDC144NL-AS1-KD human PSCs display inhibition of MAPK (ERK), accumulation of active ß-catenin, and upregulation of some LIF/STAT3 target genes, and all of these are concordant with previously reported traits of human naïve PSCs. CONCLUSIONS: Our study unveils an unexpected role of a lncRNA, CCDC144NL-AS1, in the naïve-like state conversion of human PSCs, providing a new perspective to further understand the regulation process of human early pluripotency states conversion. It is suggested that CCDC144NL-AS1 can be potentially valuable for future research on deriving higher quality naïve state human PSCs and promoting their therapeutic applications.

Biotransformation of 20(R)-panaxatriol by Mucor racemosus and the anti-hepatic fibrosis activity of some products.

Biocatalysis of 20(R)-panaxatriol (PT) was performed by the fungus Mucor racemosus. Six metabolites (1-6) including five new compounds were obtained, and their structures were elucidated as 20(R),25-epoxy-12ß,24ß-dihydroxydammaran-3,6-dione (2), 20(R),25-epoxy-12ß,22ß-dihydroxydammaran-3,6-dione (3), 20(R),25-epoxy-23ß-hydroxydammaran-3,6,12-trione (4), 20(R),25-epoxy-12ß,23α- dihydroxydammaran-3,6-dione (5), and 20(R),25-epoxy-12ß-hydroxydammaran-3,6,23-trione (6) by spectroscopic analysis. Pharmacological studies revealed that compounds 2, 3 and 5 exhibited significant antihepatic fibrosis activity, while 4 and 6 showed cytotoxicity against HSC-T6 cells.

Characterization and protective efficacy in an animal model of a novel truncated rotavirus VP8 subunit parenteral vaccine candidate.

The cell-attachment protein VP8* of rotavirus is a potential candidate parenteral vaccine. However, the yield of full-length VP8 protein (VP8*, residues 1-231) expressed in Escherichia coli was low, and a truncated VP8 protein (ΔVP8*, residues 65-231) cannot elicit efficient protective immunity in a mouse model. In this study, tow novel truncated VP8 proteins, VP8-1 (residues 26-231) and VP8-2 (residues 51-231), were expressed in E. coli and evaluated for immunogenicity and protective efficacy, compared with VP8* and ΔVP8*. As well as ΔVP8*, the protein VP8-1 and VP8-2 were successfully expressed in high yield and purified in homogeneous dimeric forms, while the protein VP8* was expressed with lower yield and prone to aggregation and degradation in solution. Although the immunogenicity of the protein VP8*, VP8-1, VP8-2 and ΔVP8* was comparable, immunization of VP8* and VP8-1 elicited significantly higher neutralizing antibody titers than that of VP8-2 and ΔVP8* in mice. Furthermore, when assessed using a mouse maternal antibody model, the efficacy of VP8-1 to protect against rotavirus-induced diarrhea in pups was comparable to that of VP8*, both were dramatically higher than that of VP8-2 and ΔVP8*. Taken together, the novel truncated protein VP8-1, with increased yield, improved homogeneity and high protective efficacy, is a viable candidate for further development of a parenterally administrated prophylactic vaccine against rotavirus infection.

Development of an enzyme-linked immunospot assay for determination of rotavirus infectivity.

Conventional rotavirus infectivity assays are time consuming, labor intensive, and with low sample throughput. To overcome these problems, a 96-well microplate enzyme-linked immunospot assay (Elispot) was developed for the measurement of rotavirus infectious titers. The infected MA104 cells were stained with a horseradish peroxidase-conjugated anti-VP6 monoclonal antibody followed by detection with an ELISPOT analyzer. A linear relationship was found between spot number and input of rotavirus dose in SA11 and 10 rotavirus isolates of different genotypes. The propagation of rotavirus SA11 in MA104 cells was monitored, and the neutralizing activity of serum samples and monoclonal antibodies was determined. The 50% neutralizing titer (NT50) of serum and 50% inhibitory concentration (IC50) of monoclonal antibodies were correlated well with the results determined by ELISA-based neutralization assay. In conclusion, a rapid and semi-automated procedure to determine rotavirus infectivity was developed, which will be useful to study the infectivity and the neutralizing epitopes of rotavirus.

Improved characteristics and protective efficacy in an animal model of E. coli-derived recombinant double-layered rotavirus virus-like particles.

Live rotavirus vaccines that are effective in middle- and high-income countries have been found to be less immunogenic and effective in infants in resource-limited settings. The virus-like particle (VLP) approach is promising for rotavirus vaccine development, but challenges remain for VLP production at large scale. In this study, rotavirus capsid VP2 and VP6 proteins were expressed in Escherichia coli and were assembled with high efficiency into homogeneous single-layered VP6-VLPs or double-layered VP2/6-VLPs (dl2/6-VLPs) through a post-purification assembly process. The dl2/6-VLPs were observed to have better thermal stability and antigenicity. Although the immunogenicity of VP6 trimers, VP6-VLPs and dl2/6-VLPs was comparable, the efficacy of the dl2/6-VLPs to protect against rotavirus-induced diarrhea in pups was significantly higher than that of the trimeric VP6 or the VP6-VLPs when assessed using a mouse maternal antibody model. Taken together, the recombinant dl2/6-VLP antigen, which is highly analogous to rotavirus virion-derived double-layered particles, is a viable candidate for vaccine development and has the potential to be a parenterally administered safe and efficacious rotavirus vaccine.