Plant diurnal oscillation is a 24-hour period based variation. The correlation between diurnal genes and biological pathways was widely revealed by microarray analysis in different species. Rice (Oryza sativa) is the major food staple for about half of the world's population. The rice flag leaf is essential in providing photosynthates to the grain filling. However, there is still no comprehensive view about the diurnal transcriptome for rice leaves. In this study, we applied rice microarray to monitor the rhythmically expressed genes in rice seedling and flag leaves. We developed a new computational analysis approach and identified 6,266 (10.96%) diurnal probe sets in seedling leaves, 13,773 (24.08%) diurnal probe sets in flag leaves. About 65% of overall transcription factors were identified as flag leaf preferred. In seedling leaves, the peak of phase distribution was from 2:00am to 4:00am, whereas in flag leaves, the peak was from 8:00pm to 2:00am. The diurnal phase distribution analysis of gene ontology (GO) and cis-element enrichment indicated that, some important processes were waken by the light, such as photosynthesis and abiotic stimulus, while some genes related to the nuclear and ribosome involved processes were active mostly during the switch time of light to dark. The starch and sucrose metabolism pathway genes also showed diurnal phase. We conducted comparison analysis between Arabidopsis and rice leaf transcriptome throughout the diurnal cycle. In summary, our analysis approach is feasible for relatively unbiased identification of diurnal transcripts, efficiently detecting some special periodic patterns with non-sinusoidal periodic patterns. Compared to the rice flag leaves, the gene transcription levels of seedling leaves were relatively limited to the diurnal rhythm. Our comprehensive microarray analysis of seedling and flag leaves of rice provided an overview of the rice diurnal transcriptome and indicated some diurnal regulated biological processes and key functional pathways in rice.

Bacillus thuringiensis (Bt), one of the most successful biopesticides, may expand its potential by producing bacteriocins (thuricins). The aim of this study was to investigate the antimicrobial potential of a novel Bt bacteriocin, thuricin BtCspB, produced by Bt BRC-ZYR2. The results showed that this bacteriocin has a high similarity with cold-shock protein B (CspB). BtCspB lost its activity after proteinase K treatment; however it was active at 60 °C for 30 min and was stable in the pH range 5-7. The partial loss of activity after the treatments of lipase II and catalase were likely due to the change in BtCspB structure and the partial degradation of BtCspB, respectively. The loss of activity at high temperatures and the activity variation at different pHs were not due to degradation or large conformational change. BtCspB did not inhibit four probiotics. It was only active against B. cereus strains 0938 and ATCC 10987 with MIC values of 3.125 μg/mL and 0.781 μg/mL, and MBC values of 12.5 μg/mL and 6.25 μg/mL, respectively. Taken together, these results provide new insights into a novel cold shock protein-like bacteriocin, BtCspB, which displayed promise for its use in food preservation and treatment of B. cereus-associated diseases.

Iron is known to be a crucial regulator of glucose, and several studies have demonstrated that iron overload is one of the risk factors for insulin resistance and diabetes; however, the mechanism has not yet been clarified. To investigate the effect of iron overload on glucose metabolism and the underlying mechanism, Irp2 knockout (Irp2-/-) mice (endogenous iron overload model) were used. We found that Irp2-/- mice exhibited hyperglycemia and iron overload in the liver and skeletal muscle. Increased MDA, decreased SOD levels, and increased cell apoptosis were also found in the liver and muscle of Irp2-/- mice. Glucose concentrations were significantly higher in Irp2-/- mice in insulin tolerance tests. However, early-phase insulin secretion was not altered in Irp2-/- mice. The expression of hepatic IRS2 and muscle GLUT4 was declined in Irp2-/- mice at both mRNA and protein levels when compared with those of wild-type control. In conclusions, Irp2-/- mice showed hyperglycemia, which might due to insulin resistance rather than due to impaired insulin secretion.

Calligonum mongolicum is a successful pioneer shrub to combat desertification, which is widely used for vegetation restoration in the desert regions of northwest China. In order to reveal the limitations to natural regeneration of C. mongolicum by asexual and sexual reproduction, following the process of sand dune stabilization, we assessed clonal shoots, seedling emergence, soil seed bank density, and soil physical characteristics in mobile and stabilized sand dunes. Controlled field and pot experiments were also conducted to assess germination and seedling emergence in different dune soil types and seed burial depths. The population density of mature C. mongolicum was significantly different after sand dune stabilization. Juvenile density of C. mongolicm was much lower in stabilized sand dunes than mobile sand dune. There was no significant difference in soil seed bank density at three soil depths between mobile and stabilized sand dunes, while the emergence of seedlings in stabilized dunes was much lower than emergence in mobile dunes. There was no clonal propagation found in stabilized dunes, and very few C. mongolicum seedlings were established on stabilized sand dunes. Soil clay and silt content, air-filled porosity, and soil surface compaction were significantly changed from mobile sand dune to stabilized dunes. Seedling emergence of C. mongolicm was highly dependent on soil physical condition. These results indicated that changes in soil physical condition limited clonal propagation and seedling emergence of C. mongolicum in stabilized sand dunes. Seed bank density was not a limiting factor; however, poor seedling establishment limited C. mongolicum's further natural regeneration in stabilized sand dunes. Therefore, clonal propagation may be the most important mode for population expansion in mobile sand dunes. As a pioneer species C. mongolicum is well adapted to propagate in mobile sand dune conditions, it appears unlikely to survive naturally in stabilized sand dune plantations.

The aim of the present study was to investigate the differential biological characteristics between cancer-associated fibroblasts (CAFs) and peri-tumor fibroblasts (PTFs) in tongue squamous cell carcinoma (TSCC). The primary CAFs and PTFs from TSCC were obtained and purified. Cell morphology was observed, and the expression of α-smooth muscle actin (α-SMA), vimentin and cytokeratin 19 (CK19) was detected by immunohistochemistry (IHC). The percentage of α-SMA positive cells in CAFs and PTFs was calculated separately, and α-SMA expression was further confirmed by western blot analysis. Cell viability and the expression of matrix metalloproteinase 2 (MMP2), stromal cell derived factor1 (SDF-1) and transforming growth factor β1 (TGFβ1) in the purified fibroblasts was detected separately. CAFs and PTFs were attained and purified. Compared with PTFs, CAFs were long-fusiform shaped cells with reduced cytoplasm and variable size. CAFs crowded together in a disorderly manner when the cell density was increased, but this phenomenon did not occur with PTFs. IHC results verified that there was no significant difference between CAFs and PTFs in the percentage of cells staining positive for CK19 and vimentin (P>0.05); the percentage of positive staining cells for α-SMA in CAFs was significantly higher compared with that in PTFs (P<0.001) Western blot analysis showed that α-SMA expression in CAFs was 4.3-fold higher compared with that in PTFs (P<0.001). A Cell Counting Kit-8 assay indicated that the viability of CAFs increased significantly compared with that in the PTFs (P<0.05). Reverse transcription-quantitative polymerase chain reaction and ELISA analysis showed that the expression of MMP2, SDF-1 and TGF β1 in CAFs was higher compared with that in PTFs (P<0.05). CAFs are distinguishable from PTFs with respect to their morphology, cellular phenotype, cell viability and pro-carcinogenic cytokine expression.

High variability phonetic training (HVPT) has been found to be effective in helping adult learners acquire non-native phonetic contrasts. The present study investigated the role of temporal acoustic exaggeration by comparing the canonical HVPT paradigm without involving acoustic exaggeration with a modified adaptive HVPT paradigm that integrated key temporal exaggerations in infant-directed speech (IDS). Sixty native Chinese adults participated in the training of the English /i/ and /i/ vowel contrast and were randomly assigned to three subject groups. Twenty were trained with the typical HVPT paradigm (the HVPT group), twenty were trained under the modified adaptive approach with acoustic exaggeration (the HVPT-E group), and twenty were in the control group. Behavioral tasks for the pre- and post- tests used natural word identification, synthetic stimuli identification, and synthetic stimuli discrimination. Mismatch negativity (MMN) responses from the HVPT-E group were also obtained to assess the training effects in within- and across- category discrimination without requiring focused attention. Like previous studies, significant generalization effects to new talkers were found in both the HVPT group and the HVPT-E group. The HVPT-E group, by contrast, showed greater improvement as reflected in larger progress in natural word identification performance. Furthermore, the HVPT-E group exhibited more native-like categorical perception based on spectral cues after training, together with corresponding training-induced changes in the MMN responses to within- and across- category differences. These data provide the initial evidence supporting the important role of temporal acoustic exaggeration with adaptive training in facilitating phonetic learning and promoting brain plasticity at the perceptual and pre-attentive neural levels.

Overexpression of Bmi1 gene is an important feature of cancer stem cell in various human tumors. Therefore, Bmi1 gene can be a potential target for small interfering RNA (siRNA) mediated cancer therapy. Ursolic acid (UA) as a natural product plays a pivotal role in anti-tumor field, although its performance is limited by low bioavailability and poor hydrophilicity. A folate receptor-targeted cationic liposome system was designed for the purpose of investigating the relationship between Bmil siRNA and UA. The folate receptor-targeted cationic liposomes co-delivering UA and Bmi1 siRNA (FA-UA/siRNA-L) were fabricated by electrostatic interaction between folate UA liposome (FA-UA-L) and Bmi1 siRNA. Tumor growth is inhibited by FA-UA/siRNA-L in vitro and in vivo and this inhibition is contributed by a synergistic anti-tumor effect of UA and Bmi1 siRNA. The western blot measurement of apoptosis-protein and cancer stem cell (CSC) marked-protein demonstrated that UA led to activation-induced tumor cell death and Bmi1 siRNA resulted in inhibition of cancer stem cells. Overall, these results indicate that Bmi1 as a regulating gene for cancer stem cell is an effective target for cancer treatment using siRNA and co-delivery of UA and Bmi1 siRNA using folate-targeted liposomes is a promising strategy for improved anti-tumor effect.

Up-regulation of Uridine-cytidine kinase 2 (UCK2), a rate-limiting enzyme of the pyrimidine salvage pathway, has been suggested in HCC, but the detailed molecular mechanisms and therapic role of UCK2 remain elusive. Bioinformatic analyses revealed that UCK2 might be a key up-regulated metabolic gene in HCCs. The expressional pattern and prognostic value of UCK2 were further examined in a large number of clinical samples. Functional assays based on site-directed mutagenesis showed that UCK2 promoted cell proliferation in a metabolic manner, but non-catalytically facilitates HCC metastasis. Mechanistically, in response to EGF, UCK2 interacted with EGFR to block EGF-induced EGFR ubiquitination and degradation, which resulted in elevated EGFR-AKT pathway activation and metastasis enhancement in HCCs. Concurrent pharmacological targeting on UCK2 and EGFR showed synergistic effects on HCC treatment. This study disclosed the non-metabolic role of UCK2 and suggested the therapeutic potential of concurrent blocking the metabolic and non-metabolic roles of UCK2 in HCC treatment.

For the time-consuming and stressful body measuring task of Qinchuan cattle and farmers, the demand for the automatic measurement of body dimensions has become more and more urgent. It is necessary to explore automatic measurements with deep learning to improve breeding efficiency and promote the development of industry. In this paper, a novel approach to measuring the body dimensions of live Qinchuan cattle with on transfer learning is proposed. Deep learning of the Kd-network was trained with classical three-dimensional (3D) point cloud datasets (PCD) of the ShapeNet datasets. After a series of processes of PCD sensed by the light detection and ranging (LiDAR) sensor, the cattle silhouettes could be extracted, which after augmentation could be applied as an input layer to the Kd-network. With the output of a convolutional layer of the trained deep model, the output layer of the deep model could be applied to pre-train the full connection network. The TrAdaBoost algorithm was employed to transfer the pre-trained convolutional layer and full connection of the deep model. To classify and recognize the PCD of the cattle silhouette, the average accuracy rate after training with transfer learning could reach up to 93.6%. On the basis of silhouette extraction, the candidate region of the feature surface shape could be extracted with mean curvature and Gaussian curvature. After the computation of the FPFH (fast point feature histogram) of the surface shape, the center of the feature surface could be recognized and the body dimensions of the cattle could finally be calculated. The experimental results showed that the comprehensive error of body dimensions was close to 2%, which could provide a feasible approach to the non-contact observations of the bodies of large physique livestock without any human intervention.

An efficient electromagnetic interference (EMI) shielding paper with excellent water repellency and mechanical flexibility has been developed, by assembling silver nanowires (AgNWs) and hydrophobic inorganic ceramic on the cellulose paper, via a facile dip-coating preparation. Scanning electron microscope (SEM) observations confirmed that AgNWs were interconnected and densely coated on both sides of the cellulose fiber, which endows the as-prepared paper with high conductivity (33.69 S/cm in-plane direction) at a low AgNW area density of 0.13 mg/cm2. Owing to multiple reflections and scattering between the two outer highly conductive surfaces, the obtained composite presented a high EMI shielding effectiveness (EMI SE) of up to 46 dB against the X band, and ultrahigh specific EMI SE of 271.2 dB mm-1. Moreover, the prepared hydrophobic AgNW/cellulose (H-AgNW/cellulose) composite paper could also maintain high EMI SE and extraordinary waterproofness (water contact angle > 140°) by suffering dozens of bending tests or one thousand peeling tests. Overall, such a multifunctional paper might have practical applications in packaging conductive components and can be used as EMI shielding elements in advanced application areas, even under harsh conditions.

This study aimed to identify small molecules that have the potential to treat alpha1-antitrypsin deficiency (AATD) by screening compounds available from a mixture-based scaffold library. 93 scaffold libraries (total diversity of >30 million compounds in mixture format) were screened using a cell model of AATD in order to identify samples that could either reduce intracellular aggregation of Z-form AAT protein, increase extracellular secretion of Z-AAT or both. Mixture libraries containing compounds with in vitro activity, for example library 1295, were screened further to identify individual active compounds. The mixture format of the scaffold library allowed for some preliminary structure-activity relationships to be developed and also enabled the rapid selection of a promising scaffold. Utilizing this scaffold, 1295, a collection of individual "control" compounds contained in the 1295 mixture sample were then screened. A sub-library of individual "control" compounds featuring structural diversity at position R1 (1295.R1), was screened and 7 compounds were found to reduce the intracellular accumulation of Z-AAT without affecting cell viability at a concentration of 25ug/ml (about 50 μM). Screening sub-libraries featuring structural diversity at R2 and R3 (1295.R2 and 1295.R3) identified an additional 15 active compounds. Titration experiments identified 3 compounds from the 1295.R2 library that retained activity at 5ug/ml (approx. 10uM). One compound (1295.263) from 1295.R2 decreased intracellular levels of Z-AAT without affecting cell viability and wild-type AAT levels at the concentration of 5ug/ml. Molecular docking of this compound to the Z-AAT crystal structure identified a potential binding site near the C-terminal domain, an identified polymerization site. Our results indicate that screening large mixture-based compound libraries can be used to identify small molecules that may have the potential to treat AATD and other disease.

Cholangiocarcinoma (CCA) is an epithelial cancer and has high death and recurrence rates, current methods cannot satisfy the need for predicting cancer relapse effectively. So, we aimed at conducting a multi-mRNA signature to improve the relapse prediction of CCA. We analyzed mRNA expression profiling in large CCA cohorts from the Gene Expression Omnibus (GEO) database (GSE76297, GSE32879, GSE26566, GSE31370, and GSE45001) and The Cancer Genome Atlas (TCGA) database. The Least absolute shrinkage and selection operator (LASSO) regression model was used to establish a 7-mRNA-based signature that was significantly related to the recurrence-free survival (RFS) in two test series. Based on the 7-mRNA signature, the cohort TCGA patients could be divided into high-risk or low-risk subgroups with significantly different RFS [p < 0.001, hazard ratio (HR): 48.886, 95% confidence interval (CI): 6.226-3.837E+02]. Simultaneously, the prognostic value of the 7-mRNA signature was confirmed in clinical samples of Ren Ji hospital (p < 0.001, HR: 4.558, 95% CI: 1.829-11.357). Further analysis including multivariable and sub-group analyses revealed that the 7-mRNA signature was an independent prognostic value for recurrence of patients with CCA. In conclusion, our results might provide an efficient tool for relapse prediction and were beneficial to individualized management for CCA patients.

Sclerotinia sclerotiorum, one of the major diseases infecting oilseed rape leaves, has seriously affected crop yield and quality. In this study, an indoor unmanned aerial vehicle (UAV) low-altitude remote sensing simulation platform was built for disease detection. Thermal, multispectral and RGB images were acquired before and after being artificially inoculated with Sclerotinia sclerotiorum on oilseed rape leaves. New image registration and fusion methods based on scale-invariant feature transform (SIFT) were presented to construct a fused database using multi-model images. The changes of temperature distribution in different sections of infected areas were analyzed by processing thermal images, the maximum temperature difference (MTD) on a single leaf reached 1.7 degrees Celsius 24 h after infection. Four machine learning models were established using thermal images and fused images respectively, including support vector machine (SVM), random forest (RF), K-nearest neighbor (KNN) and naïve Bayes (NB). The results demonstrated that the classification accuracy was improved by 11.3% after image fusion, and the SVM model obtained a classification accuracy of 90.0% on the task of classifying disease severity. The overall results indicated the UAV low-altitude remote sensing simulation platform equipped with multi-sensors could be used to early detect Sclerotinia sclerotiorum on oilseed rape leaves.

Plasma lipids have been at the center stage of the prediction and prevention strategies for cardiovascular diseases (CVDs), and novel lipidomic traits have been recognized as reliable biomarkers for CVD risk prediction. The mitochondria serve as energy supply sites for cells and can synthesize a variety of lipids autonomously. Therefore, investigating the relationships between mitochondrial single nucleotide polymorphism (SNPs) and plasma lipidomic traits is meaningful. Here, we enrolled a total of 1,409 Han Chinese patients with coronary artery disease from three centers and performed linear regression analyses on the SNPs of mitochondrial DNA (mtDNA) and lipidomic traits in two independent groups. Sex, age, aspartate aminotransferase, estimated glomerular filtration rate, antihypertensive drugs, hypertension, and diabetes were adjusted. We identified three associations, namely, D-loop m.16089T>C with TG(50:4) NL-16:0, D-loop m.16145G>A with TG(54:5) NL-18:0, and D-loop m.16089T>C with PC(16:0_16:1) at the statistically significant threshold of FDR < 0.05. Then, we explored the relationships between mitochondrial genetic variants and traditional lipids, including triglyceride, total cholesterol (TC), low-density lipoprotein cholesterol (LDLC), and high-density lipoprotein cholesterol. Two significant associations were found, namely MT-ND6 m.14178T>C with TC and D-loop m.215A>G with LDLC. Furthermore, we performed linear regression analysis to determine on the SNPs of mtDNA and left ventricular ejection fraction (LVEF) and found that the SNP D-loop m.16145G>A was nominally significantly associated with LVEF (P = 0.047). Our findings provide insights into the lipidomic context of mtDNA variations and highlight the importance of studying mitochondrial genetic variants related to lipid species.

Congenital heart disease (CHD) is the most common birth defect. The prenatal diagnosis of fetal CHD is completely dependent on ultrasound testing, but only ~40% of CHD can be detected. The purpose of this study is to find good biomarkers in amniotic fluid (AF) to detect CHD in the second trimester, so as to better manage this group of people and reduce the harm of CHD to the fetus. Metabolites analysis were performed in two separate sets. The discovery set consisted of 18 CHD fetal maternal AF samples and 35 control samples, and the validation set consisted of 53 CHD fetal maternal AF samples and 114 control samples. Untargeted metabolite profiles were analyzed by gas chromatography/time-of-flight-mass spectrometry (GC-TOF/MS). Orthogonal partial least square discrimination analysis (OPLS-DA) demonstrated that CHD and control samples had significantly different metabolic profiles. Two metabolites, uric acid and proline, were significantly elevated in CHD and verified in two data sets. Uric acid was associated with CHD [odds ratio (OR): 7.69 (95% CI: 1.18-50.13) in the discovery set and 3.24 (95% CI:1.62-6.48) in the validation set]. Additionally, uric acid showed moderate predictive power; the area under curve (AUC) was 0.890 in the discovery set and 0.741 in the validation set. The sensitivity and specificity of uric acid to detect CHD was, respectively, 94.4 and 74.3% in the discovery set and 67.9 and 71.9% in the validation set. The identification of uric acid as a biomarker for CHD has the potential to stimulate research on the pathological mechanism of CHD and the development of a diagnostic test for clinical applications.

Mitochondrial transplantation emerges as a novel therapeutic solution for ischemia/reperfusion injury (IRI) in various tissues. Platelets have recently been used in mitochondrial transplantation as readily-available donors of small-size platelet mitochondria (plt-mito). Interestingly, FUN14 Domain Containing 2 (FUNDC2), a protein highly-expressed in the outer membrane (OMM) of plt-mito, has been identified to maintain platelet survival under hypoxic condition. The current study determined whether and how FUNDC2 contributed to the therapeutic effect of plt-mito transplantation for hypoxia/reoxygenation (HR) injury. The results showed that incorporation of human plt-mito into SH-SY5Y cells rescued HR-induced mitochondrial malfunction and mitochondrial apoptotic pathway. Mechanistically, plt-mito transplantation led to an increased expression of FUNDC2 in the recipient cells. This protein induced mitochondrial translocation of phosphatidylinositol-3,4,5-trisphosphate (PIP3) via its N-term, resulting in the stimulation of the protein kinase B (Akt)/forkhead box O3a (FOXO3a) pathway, which inhibited HR-induced mitochondrial accumulation of a mitochondrial target of FOXO3a, Bim, also known as a pro-apoptotic protein. Therefore, the FUNDC2/PIP3/Akt/FOXO3a axis may facilitate the incorporated plt-mito to restore mitochondrial function and cell viability of the recipient cells, and platelets may serve as readily-available sources of donor mitochondria that afford therapeutic benefits against IRI.

The differentiation of lymphatic progenitors is a crucial step in lymphangiogenesis. However, its underlying mechanism remains unclear. Here, we found that noncanonical protease-activated receptor 1 (par1) regulates the differentiation of lymphatic progenitors in zebrafish embryos. Loss of par1 function impaired lymphatic differentiation by downregulating prox1a expression in parachordal lymphangioblasts and caused compromised thoracic duct formation in zebrafish. Meanwhile, the G protein gnai2a, a par1 downstream effector, was selectively required for lymphatic development in zebrafish, and its mutation mimicked the lymphatic phenotype observed in par1 mutants. Interestingly, mmp13, but not thrombin, was required for lymphatic development in zebrafish. Furthermore, analyses of genetic interactions confirmed that mmp13b serves as a par1 upstream protease to regulate lymphatic development in zebrafish embryos. Mechanistically, par1 promotes flt4 expression and phospho-Erk1/2 activity in the posterior cardinal vein. Taken together, our findings highlight a function of par1 in the regulation of lymphatic differentiation in zebrafish embryos.

There are more than 100 species of American didelphid marsupials (opossums and mouse opossums). Limited genomic resources for didelphids exists, with only two publicly available genome assemblies compared with dozens in the case of their Australasian counterparts. This discrepancy impedes evolutionary and ecological research. To address this gap, we assembled a high-quality chromosome-level genome of the agile gracile mouse opossum (Gracilinanus agilis) using a combination of stLFR sequencing, polishing with mate-pair data, and anchoring onto pseudochromosomes using Hi-C. This species employs a rare life-history strategy, semelparity, and all G. agilis males and most females die at the end of their first breeding season after succumbing to stress and exhaustion. The 3.7-Gb chromosome-level assembly, with 92.6% anchored onto pseudochromosomes, has a scaffold N50 of 683.5 Mb and a contig N50 of 56.9 kb. The genome assembly shows high completeness, with a mammalian BUSCO score of 88.1%. Around 49.7% of the genome contains repetitive elements. Gene annotation yielded 24,425 genes, of which 83.9% were functionally annotated. The G. agilis genome is an important resource for future studies of marsupial biology, evolution, and conservation.

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. However, there is still no single drug that could reduce septic mortality. Previous studies have reported gabexate mesylate (GM) significantly reduced serum inflammatory factors, alleviated sepsis-induced lung injury and improved clinical outcomes. This study aimed to combine with microbiome sequencing and metabolomics analysis to explore the effects of GM administration in septic rats.

Neutrophil elastase (NE) is associated with sepsis occurrence and progression. We hypothesized that the NE inhibitor Sivelestat might modulate abnormal gut microbiota and metabolites during sepsis.