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Discovering more novel antimicrobial compounds has become a keen research problem. In this study, YA215 genome was sequenced by the Illumina HiSeq + PacBio sequencing platform. Genome assembly was performed by Unicycler software and the gene clusters responsible for secondary metabolite biosynthesis were predicted by antiSMASH. The genome comprised 3976514 bp and had a 46.56% G + C content. 3809 coding DNA sequences, 27 rRNAs, 86 tRNAs genes, and 79 sRNA were predicted. Strain YA215 was re-identified as Bacillus velezensis based on ANI and OrthoANI analysis. In the COG database, 23 functional groups from 3090 annotations were predicted. In the GO database, 2654 annotations were predicted. 2486 KEGG annotations linked 41 metabolic pathways. Glycosyl transferases, polysaccharide lyases, auxiliary activities, glycoside hydrolases, carbohydrate esterases, and carbohydrate-binding modules were predicted among the 127 annotations in the CAZy database. AntiSMASH analysis predicted that B. velezensis YA215 boasted 13 gene clusters involved in synthesis of antimicrobial secondary metabolites including surfactin, fengycin, macrolactin H, bacillaene, difficidin, bacillibactin, bacilysin, and plantazolicin. Three of the gene clusters (gene cluster 5, gene cluster 9, and gene cluster 10) have the potential to synthesize unknown compounds. The research underscore the considerable potential of secondary metabolites, identified in the genomic composition of B. velezensis YA215, as versatile antibacterial agents with a broad spectrum of activity against pathogenic bacteria. [ABSTRACT FROM AUTHOR]

Unsupervised semantic segmentation (USS) aims at partitioning an image into semantically meaningful segments by learning from a collection of unlabeled images. The effectiveness of current approaches is plagued by difficulties in coordinating representation learning and pixel clustering, modeling the varying feature distributions of different classes, handling outliers and noise, and addressing the pixel class imbalance problem. This paper introduces a novel approach, termed Imbalance-Aware Dense Discriminative Clustering (IDDC), for USS, which addresses all these difficulties in a unified framework. Different from existing approaches, which learn USS in two stages (i.e., generating and updating pseudo masks, or refining and clustering embeddings), IDDC learns pixel-wise feature representation and dense discriminative clustering in an end-to-end and self-supervised manner, through a novel objective function that transfers the manifold structure of pixels in the embedding space of a vision Transformer (ViT) to the label space while tolerating the noise in pixel affinities. During inference, the trained model directly outputs the classification probability of each pixel conditioned on the image. In addition, this paper proposes a new regularizer, based on the Weibull function, to handle pixel class imbalance and cluster degeneration in a single shot. Experimental results demonstrate that IDDC significantly outperforms all previous USS methods on three real-world datasets, COCO-Stuff-27, COCO-Stuff-171, and Cityscapes. Extensive ablation studies validate the effectiveness of each design. Our code is available at https://github.com/MY-LIU100101/IDDC. [ABSTRACT FROM AUTHOR]

Antibiotics are essential for combating pathogens; however, their misuse has led to increased resistance, necessitating the search for effective, low-toxicity alternatives. Surfactin, a cyclic lipopeptide with a C12-C17 β-hydroxy fatty acid chain, exhibits significant antibacterial activity and resists resistance, making it a research focus. Nonetheless, the effects of branched-chain amino acids (BCAAs) on surfactin's structure and activity are not well understood. This study examines the influence of BCAAs (L-valine, L-leucine, and L-isoleucine) on the lipopeptide (surfactin) produced by Bacillus velezensis YA215. Process optimization shows that adding 1 g/L of L-Leu and L-Ile, and 0.5 g/L of L-Val, maximized surfactin production to 18.59%, 19.23%, and 20.64%, respectively. Surfactin content peaked at 36 h with L-Val and L-Ile, yielding 19.72% and 11.37%. In contrast, L-Leu addition peaked at 24 h, yielding 11.33%. Notably, L-Val supplementation resulted in the highest relative surfactin content. Antimicrobial testing demonstrated that BCAAs significantly enhance the antibacterial effects of lipopeptides against Escherichia coli and Staphylococcus aureus, with Val showing the most pronounced effect. The addition of BCAAs notably altered the composition of surfactin fatty acid chains. Specifically, Val increased the proportions of iso C14 and iso C16 β-hydroxy fatty acids from 13.3% and 4.216–23.803% and 8.31%, respectively. Additionally, the amino acid composition at the 7th position of the peptide chain changed significantly, especially with Val addition, which increased the proportion of C14 [Val 7] surfactin by 3.29 times. These structural changes are likely associated with the enhanced antibacterial activity of surfactin. These findings provide valuable insights into the roles of BCAAs in microbial fermentation, underscoring their importance in metabolic engineering to enhance the production of bioactive compounds. [ABSTRACT FROM AUTHOR]

The soil leaching process for efficient heavy metal-contaminated soil remediation is usually completed with mud-water separation. However, the influence of mud-water separation on the removal effect of heavy metals is little known. The study aims to investigate the linkage effect of soil leaching and flocculation dewatering on mud flocculation and heavy metal removal, and the mechanism was investigated. The results showed that sequential leaching of contaminated soil with oxalic acid-citric acid-Na2EDTA resulted in 57.0%, 59.8%, 35.7%, and 76.4% removal of heavy metals Zn, Cu, Pb, and Ni, respectively. In the process of sequential leaching combined with flocculation and dewatering, the desirable mud-water separation could be obtained when 130 mg·L−1 of CPAM was added, with the absolute value of zeta potential being 0.59 mV, the turbidity of the residual water reducing to 14.7 NTU, the floc settling time being 72 s, and the floc median particle size being 33.375 mm. Compared with the single sequential leaching, the heavy metal Zn and Pb removal rates increased by 6.0% and 10.5%, respectively. The analysis of the linkage effect mechanism shows that both organic acid complexation and displacement of heavy metals on mud particles by CPAM contribute to the removal of heavy metals, while CPAM compresses the thickness of the electric double layer on the surface of the mud particles, which makes some heavy metals in weakly adsorbed water enter into the free water. This study provides a useful reference for optimizing the ex-situ remediation process of heavy metal-contaminated soil. [ABSTRACT FROM AUTHOR]

High concentrations of organic aerosol (OA) occur in Asian countries, leading to great health burdens. Clean air actions have resulted in significant emission reductions of air pollutants in China. However, long-term nation-wide trends in OA and their causes remain unknown. Here, we present both observational and model evidence demonstrating widespread decreases with a greater reduction in primary OA than in secondary OA (SOA) in China during the period of 2013 to 2020. Most of the decline is attributed to reduced residential fuel burning while the interannual variability in SOA may have been driven by meteorological variations. We find contrasting effects of reducing NOx and SO2 on SOA production which may have led to slight overall increases in SOA. Our findings highlight the importance of clean energy replacements in multiple sectors on achieving air-quality targets because of high OA precursor emissions and fluctuating chemical and meteorological conditions.Clean air actions affect air quality greatly. Here, the authors report widespread decreases in organic aerosol (OA) in China from 2013 to 2020 with primary OA decreasing more than secondary OA. However, further reductions are challenging. [ABSTRACT FROM AUTHOR]

Satellite clock bias (SCB) is a critical factor influencing the accuracy of real-time precise point positioning. Nevertheless, the utilization of real-time service products, as supplied by the International GNSS Service, may be vulnerable to interruptions or network failures. In specific situations, users may encounter difficulties in obtaining accurate real-time corrections. Our research presents an enhanced predictive model for SCB using a long short-term memory (LSTM) neural network fused with a Self-Attention mechanism to address this challenge. This fusion enables the model to effectively balance global attention and localized feature capture, ultimately enhancing prediction accuracy and stability. We compared and analyzed our proposed model with convolutional neural network (CNN) and LSTM models. This analysis encompasses an assessment of the model's strengths and suitability for predicting SCB within the BeiDou navigation system, considering diverse satellites, orbits, and atomic clocks. Our results exhibit a substantial improvement in predictive accuracy through the LSTM-Attention model. There has been an improvement of 49.67 and 62.51% compared to the CNN and LSTM models in the 12-h prediction task. In the case of the 24-h prediction task, the improvements escalated to 68.41 and 71.16%, respectively. [ABSTRACT FROM AUTHOR]

Quantizing is a promising approach to facilitate deploying deep neural networks on resource-limited devices. However, existing methods are challenged by obtaining computation acceleration and parameter compression while maintaining excellent performance. To achieve this goal, we propose PSE, a mixed quantization framework which combines product quantization (PQ), scalar quantization (SQ), and error correction. Specifically, we first employ PQ to obtain the floating-point codebook and index matrix of the weight matrix. Then, we use SQ to quantize the codebook into integers and reconstruct an integer weight matrix. Finally, we propose an error correction algorithm to update the quantized codebook and minimize the quantization error. We extensively evaluate our proposed method on various backbones, including VGG-16, ResNet-18/50, MobileNetV2, ShuffleNetV2, EfficientNet-B3/B7, and DenseNet-201 on CIFAR-10 and ILSVRC-2012 benchmarks. The experiments demonstrate that PSE reduces computation complexity and model size with acceptable accuracy loss. For example, ResNet-18 achieves 1.8 × acceleration ratio and 30.4 × compression ratio with less than 1.54% accuracy loss on CIFAR-10. [ABSTRACT FROM AUTHOR]

Fluorescence micro-optical sectioning tomography (fMOST) is a three-dimensional (3d) imaging method at the mesoscopic level. The whole-brain of mice can be imaged at a high resolution of 0.32 × 0.32 × 1.00 μm3. It is useful for revealing the fine morphology of intact organ tissue, even for positioning the single vessel connected with a complicated vascular network across different brain regions in the whole mouse brain. Featuring its 3d visualization of whole-brain cross-scale connections, fMOST has a vast potential to decipher brain function and diseases. This article begins with the background of fMOST technology including a widespread 3D imaging methods comparison and the basic technical principal illustration, followed by the application of fMOST in cerebrovascular research and relevant vascular labeling techniques applicable to different scenarios. [ABSTRACT FROM AUTHOR]

Fumonisin B1 (FB1) is one of the important mycotoxins posing health risks in the area of food safety. A sensitive fluorescence ratio immunoassay has been established for FB1 based on the growth of monodispersed 2-D MnO2 nanosheet on an individual gold nanoparticle (AuNP@MnO2). FB1 competed with the coated FB1-BSA to bind the FB1 monoclonal antibody. After a washing step, alkaline phosphatase-labeled goat anti-mouse IgG (ALP-IgG) with high catalytic activity was combined with FB1 monoclonal antibody. ALP reacts with ascorbic acid 2-phosphate (AAP) to produce ascorbic acid (AA), which decomposes AuNP@MnO2 to dehydroascorbic acid (DHAA). O-Phenylenediamine dihydrochloride (OPD) is oxidized to yellow-fluorescent substrate of 2,3-diaminophenazine (DAP) (excitation, 423 nm; emission, 570 nm) by AuNP@MnO2. Meanwhile, OPD can also be reduced to blue fluorescent substrate of OPDred (excitation, 350 nm; emission, 430 nm) by DHAA. The content of FB1 can be determined by fluorescence ratio of blue/yellow. The limit of detection (LOD) of the fluorescence ratio immunoassay for FB1 was 0.06 ng mL−1, and the linear range was from 0.25 to 60.00 ng mL−1. The effectiveness of the assay was verified in real maize samples, and satisfactory recoveries were attained. The correlation coefficient of these results between the fluorescence ratio immunoassay and commercial ELISA kit was 0.9999. This method provides a sensitive and selective tool for the detection of FB1 in maize samples. [ABSTRACT FROM AUTHOR]

Concurrent multipath transfer (CMT) has been proved to significantly improve the end-to-end throughput with its multihoming property. However, due to the extremely high unpredictability around high-speed railway (HSR) environment, the receive buffer blocking problem seriously degrades the overall transmission reliability. To address this issue, this paper proposes a learning-based fountain coding for CMT (FC-CMT) scheme to mitigate the negative influence of the path diversity of HSR networks. Specifically, we first formulate a multi-dimensional optimal problem to mitigate receive buffer blocking phenomenon and improve the transmission rate with requirement constrains. Then, we transform the data scheduling and redundancy coding rate problem into a Markov decision process, and propose a deep reinforcement learning (DRL)-based fountain coding algorithm to dynamically adjust data scheduling policy and redundancy coding rate. We conduct the extensive experiments in a P4-based programmable network platform. Experimental results indicate the proposed algorithm mitigates the packet out-of-order problem, and improves the average throughput compared with traditional multipath transmission scheme. [ABSTRACT FROM AUTHOR]

The purpose was to explore the value of high on-treatment platelet reactivity (HTPR) in predicting long-term clinical outcomes for stroke patients. The platelet reactivity was assayed after being treated with either 75 mg clopidogrel or 100 mg aspirin daily with VerifyNow System in stroke patients. HTPR for clopidogrel was defined as PRU ≥ 208, and that for aspirin was defined as ARU ≥ 550. CYP2C19 genotyping was performed using the Sequenom MassARRAY iPLEX platform. The primary endpoint was a composite of recurrent ischemic stroke, transient ischemic attack, myocardial infarction, or ischemic vascular death. The safety endpoint was bleeding. In the clopidogrel group, among 345 patients recruited, 174 of them were categorized as HTPR. A total of 270 patients were followed up for 54 months. There was a significant association between HTPR and the primary endpoint (HRadj 2.13 [95% CI, 1.43–3.15], p < 0.001). Among the 314 participants genotyped for CYP2C19, 187 (59.6%) were classified as CYP2C19 loss-of-function allele carriers. Patients with at least 1 loss-of-function allele were more likely to present with HTPR (ORadj 2.61 [95%CI, 1.43–4.77], p = 0.008), and had a higher risk of the primary endpoint (HRadj 2.05 [95% CI, 1.30, 3.25], p = 0.002). In the aspirin group, among 140 patients recruited, 28 of them were categorized as HTPR. A total of 121 patients were followed up for 30 months. Similarly, there was a significant association between HTPR and the primary endpoint (HRadj 3.28 [95% CI, 1.52–7.71], p = 0.002). HTPR is an independent risk factor for ischemic events during long-term follow-up in stroke patients. Platelet function testing is helpful to evaluate the effect of antiplatelet therapy for stroke patients. [ABSTRACT FROM AUTHOR]

In amorphous InAlZnO (a-IAZO), the addition of the third cation of Al further slows the crystallization kinetics of In2O3 and enhances amorphous phase stability, compared to the binary cation system of InZnO. In addition, substantially high carrier mobilities of a-IAZO are obtained, in its unannealed state: Hall mobility of 30–50 cm2/Vs at a high carrier density regime (>~1018/cm3) and thin film transistor (TFT) field effect mobility of ~8–15 cm2/Vs at a low carrier density regime (<~1016/cm3). Gate bias stress stability of IAZO TFTs is investigated with positive and negative gate biases over time. Because of the channel depletion of n-type IAZO when negative gate bias is applied, no performance instabilities were identified. However, with positive gate bias stress (PBS) conditions (30 V), the threshold voltage (VT) shifts towards higher voltages during the initial 100 s and then no significant changes in VT are observed during the remaining time, over 105 s of the dependent measurements. The TFT field effect mobility shows a similar trend: increases from 7.64 cm2/Vs to 11.74 cm2/Vs within the first 100 s and then is saturated. It is identified that the PBS-induced device parameter variations are attributed to an increase and saturation of trap density at the channel/dielectric interface. [ABSTRACT FROM AUTHOR]

Taenia and Trichinella parasites are globally distributed foodborne zoonotic pathogens transmitted from animal to humans via consumption of raw or undercooked meats. This short review is intended to provide the parasites community a snapshot of the literature on the current and recent prevalence of taeniasis and trichinellosis in humans and animals in the Far East countries. Prevalence rates in these countries are highly diverse due to differences in development, culture, ethnic and religious background, animal forming practices, and eating habits. Taenia and Trichinella remain as important meat-transmitted pathogens in the Far East. A One Health approach is needed to eliminate or continuously reduce the foodborne zoonotic taeniasis and trichinellosis in the Far East. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) caused by Mycobacterium tuberculosis (M. tuberculosis) is a fatal infectious disease to human health, and the drug tolerance and immune evasion of M. tuberculosis were reported to be related to its biofilm formation; however, the difficulty of M. tuberculosis biofilm culture and its unknown global mechanism impede its further research. Here, we developed a modified in vitro M. tuberculosis biofilm model with shorter culture time. Then we used Illumina RNA-seq technology to determine the global gene expression profile of M. tuberculosis H37Rv biofilms. Over 437 genes are expressed at significantly different levels in biofilm cells than in planktonic cells; among them, 153 were downregulated and 284 were upregulated. Go enrichment analysis and KEGG pathway analysis showed that genes involved in biosynthesis and metabolism of sulfur metabolism, steroid degradation, atrazine degradation, mammalian cell entry protein complex, etc. are involved in M. tuberculosis biofilm cells. Especially, ATP-binding cassette (ABC) transporters Rv1217c and Rv1218c were significantly upregulated in biofilm, whereas efflux pump inhibitors (EPIs) piperine and 1-(1-naphthylmethyl)-piperazine (NMP) inhibited biofilm formation and the expression of the Rv1217c and Rv1218c genes in a concentration-dependent manner, respectively, indicating Rv1217c and Rv1218c are potential target genes of M. tuberculosis biofilm. This study is the first RNA-Seq-based transcriptome profiling of M. tuberculosis biofilms and provides insights into a potential strategy for M. tuberculosis biofilm inhibition. Key points: • Characterize M. tuberculosis transcriptomes in biofilm cells by RNA-seq. • Inhibit the expression of Rv1217c and Rv1218c repressed biofilm formation. [ABSTRACT FROM AUTHOR]

The formation mechanism of aerosol sulfate during wintertime haze events in China is still largely unknown. As companions, SO2 and transition metals are mainly emitted from coal combustion. Here, we argue that the transition metal-catalyzed oxidation of SO2 on aerosol surfaces could be the dominant sulfate formation pathway and investigate this hypothesis by integrating chamber experiments, numerical simulations and in-field observations. Our analysis shows that the contribution of the manganese-catalyzed oxidation of SO2 on aerosol surfaces is approximately one to two orders of magnitude larger than previously known routes, and contributes 69.2% ± 5.0% of the particulate sulfur production during haze events. This formation pathway could explain the missing source of sulfate and improve the understanding of atmospheric chemistry and climate change. Sulfate aerosols are an important component of wintertime haze events in China, but their production mechanisms are not well known. Here, the authors show that transition metal-catalyzed oxidation of SO2 on aerosol surfaces could be the dominant sulfate formation pathway in Northern China. [ABSTRACT FROM AUTHOR]

Genome assemblies provide a powerful basis of comparative multi-omics analyses that offer insight into parasite pathogenicity, host-parasite interactions, and invasion biology. As a unique intracellular nematode, Trichinella consists of two clades, encapsulated and non-encapsulated. Genomic correlation of the distinct differences between the two clades is still unclear. Here, we report an annotated draft reference genome of non-encapsulated Trichinella, T. pseudospiralis, and perform comparative multi-omics analyses with encapsulated T. spiralis. Genome and methylome analyses indicate that, during Trichinella evolution, the two clades of Trichinella exhibit differential expansion and methylation of parasitism-related multi-copy gene families, especially for the DNase II members of the phospholipase D superfamily and Glutathione S-transferases. Further, methylome and transcriptome analyses revealed divergent key excretory/secretory (E/S) genes between the two clades. Among these key E/S genes, TP12446 is significantly more expressed across three life stages in T. pseudospiralis. Overexpression of TP12446 in the mouse C2C12 skeletal muscle cell line could induce inhibition of myotube formation and differentiation, further indicating its key role in parasitism of T. pseudospiralis. This multi-omics study provides a foundation for further elucidation of the mechanism of nurse cell formation and immunoevasion, as well as the identification of pharmacological and diagnostic targets of trichinellosis. Xiaolei Liu, Yayan Feng, et al. report an annotated draft reference genome of the non-encapsulated Trichinella pseudospiralis, and perform comparative multi-omics analyses with encapsulated T. spiralis. Overexpression of TP12446, a key excretory/secretory gene, in a mouse C2C12 skeletal muscle cell line could induce inhibition of myotube formation and differentiation. These results provide insight into the mechanism of nurse cell formation and immunoevasion, as well as the identification of potential pharmacological and diagnostic targets for trichinellosis. [ABSTRACT FROM AUTHOR]

The Dynamical-microphysical-electrical Processes in Severe Thunderstorms and Lightning Hazards (STORM973) project conducted coordinated comprehensive field observations of thunderstorms in the Beijing metropolitan region (BMR) during the warm season from 2014 to 2018. The aim of the project was to understand how dynamical, microphysical and electrical processes interact in severe thunderstorms in the BMR, and how to assimilate lightning data in numerical weather prediction models to improve severe thunderstorm forecasts. The platforms used in the field campaign included the Beijing Lightning Network (BLNET, consisting of 16 stations), 2 X-band dual linear polarimetric Doppler radars, and 4 laser raindrop spectrometers. The collaboration also made use of the China Meteorological Administration's mesoscale meteorological observation network in the Beijing-Tianjin-Hebei region. Although diverse thunderstorm types were documented, it was found that squall lines and multicell storms were the two major categories of severe thunderstorms with frequent lightning activity and extreme rainfall or unexpected local short-duration heavy rainfall resulting in inundations in the central urban area, influenced by the terrain and environmental conditions. The flash density maximums were found in eastern Changping District, central and eastern Shunyi District, and the central urban area of Beijing, suggesting that the urban heat island effect has a crucial role in the intensification of thunderstorms over Beijing. In addition, the flash rate associated with super thunderstorms can reach hundreds of flashes per minute in the central city regions. The super (5% of the total), strong (35%), and weak (60%) thunderstorms contributed about 37%, 56%, and 7% to the total flashes in the BMR, respectively. Owing to the close connection between lightning activity and the thermodynamic and microphysical characteristics of the thunderstorms, the lightning flash rate can be used as an indicator of severe weather events, such as hail and short-duration heavy rainfall. Lightning data can also be assimilated into numerical weather prediction models to help improve the forecasting of severe convection and precipitation at the cloud-resolved scale, through adjusting or correcting the thermodynamic and microphysical parameters of the model. [ABSTRACT FROM AUTHOR]

Human trichinellosis is acquired by eating raw or undercooked meats carrying muscle larvae of Trichinella spp. Toll-like receptors (TLRs) are essential components of the innate immune system. However, little is known about the potential application of TLR agonists for immunotherapy against Trichinella spiralis (T. spiralis) infection. Here, we evaluated the effects of four TLR agonists (i.e., TLR3, TLR4, TLR8, and TLR9 agonists) on T. spiralis infection in mice. The reduction rate of worm burden showed that TLR3 agonist poly(I:C) significantly reduced T. spiralis infection rather than TLR4, TLR8, and TLR9 agonists (p < 0.05). Moreover, TLR3 showed a continuous high-level of expression during 6–35 days post infection (dpi). The levels of interferon-gamma (IFN-γ), interleukin (IL)-2, and IL-6 increased significantly in mice serum compared with control group after treatment with TLR3 agonist at 0, 3, 6, 9, 12, 15, 18, 21, 28, and 35 dpi (p < 0.05). A significant decreasing trend was also detected in levels of IL-10 and IL-4 after treatment with TLR3 agonist compared with control group at 0, 3, 6, 9, 12, 15, 18, 21, 28, and 35 dpi (p < 0.05). Overall, this study suggested that TLR3-targeted therapies might be effective on worm burden reduction by regulation of the cytokine levels in the mice infected with T. spiralis. [ABSTRACT FROM AUTHOR]

Salinity is a crucial environmental stress that severely affects fish growth and survival. Under environmental stress, DNA methylation plays an important role in gene expression and genome function. To better understand the epigenetic regulation mechanism of igf2 under low salinity stress, we analyzed the DNA methylation at 5′UTR, exon1, intron1, and exon2, and analyzed the relationship of DNA methylation with mRNA abundance as well as the special single CpG sites methylation patterns of igf2 in the liver of half smooth tongue sole under low salinity (15) for 0, 7, and 60 d. When exposed to low salinity, DNA methylation at 5′UTR and exon2 remained stable, while it was up-regulated firstly and then down-regulated at exon1 and intron1. Some single CpG sites of igf2 associated with low salinity, and most of these sites with significantly changed methylation levels (P 0.05) are located in intron1 area. The discrepant variation of single CpG sites methylation levels and igf2 expression further revealed that females and males showed different response to low salinity. Remarkably, the 38-CpG site of intron1 servers as a sexual marker. Additionally, our integrative analysis demonstrated that regional DNA of igf2 methylation had highly complex interplay on gene expression. The single CpG sites in intron1 were indispensable epigenetic markers under external environmental stress. Above all, to resist the low salinity stress, half smooth tongue sole liver can regulate the expression of igf2 through methylation of CpG sites in intron1. [ABSTRACT FROM AUTHOR]

Animal growth depends on feedback regulation of hormone levels and environmental conditions. Insulin-like growth factor-1 (Igf1) promotes cell growth and differentiation and represses apoptosis and is highly regulated by the environment. Moreover, animals modify physiological homeostasis under stressful conditions through epigenetics and genetic regulatory mechanisms. Therefore, a comprehensive understanding of the effects of salt on fish growth is needed. In this study, half smooth tongue sole ( Cynoglossus semilaevis) were subjected to 15‰ salinity for 0, 7, and 60 days (D) to assess the effects of low salinity on liver cellularity and growth. The results show that low salinity changed liver morphology, suggesting an increase in energy expenditure to recover from the osmotic disruption. igf1 was upregulated in female fish under 15‰ salinity after 7D and may participate in molecular repair. igf1 was downregulated after 60D of salt stress, resulting in retarded growth. Methylation levels were opposite to those of gene expression, suggesting inhibited regulation. Furthermore, three exons in the igf1 gene had significantly different methylation levels in fish under salt stress. Notably, more putative transcription factor binding sites were located in CpG sites at higher methylation levels. igf1 is not a sex-related gene, as no difference in methylation level was detected between males and females in the control group. These results clarify liver damage and changes in DNA methylation and mRNA expression of igf1, providing insight into the adverse effects of low salt on growth of C. semilaevis and the epigenetics and regulatory mechanisms involved in stressful conditions. [ABSTRACT FROM AUTHOR]

Schwann cells (SCs) proliferation is crucial for nerve regeneration following nerve injury. This study aims to investigate effects of interleukin-22 (IL-22) on SCs proliferation in vitro, as well as the corresponding mechanism. Rat SCs were treated with 100 ng/ml rat IL-22 for 48 h, and cell proliferation and apoptosis were detected using fluorescent staining and flow cytometry. After transcriptome sequencing, raw reads were filtered and mapped to reference genome rn5. Then, differentially expressed genes (DEGs) and long non-coding RNAs (DElncRNAs) between IL-22 and control groups were identified (tool: Cuffdiff). Functional and pathway enrichment analyses were performed (tool: GOFunction), and protein-protein interaction (PPI) network was constructed (tool: STRING and Cytoscape). Furthermore, Pearson's correlations between DEGs and DElncRNAs were analyzed, and regulatory network of DEGs, DElncRNAs, and transcription factors (TFs) was constructed. IL-22 significantly inhibited proliferation ( p value < 0.05) and promoted apoptosis of Schwann cells. Totally, 932 DEGs and 118 DElncRNAs were identified, among which Ccl2 and Ccna2 were hub genes in PPI network. Up-regulated DEGs were enriched in apoptosis related terms, whereas down-regulated DEGs were enriched in proliferation related terms. DElncRNAs like NONRATT023505, NONRATG020400, and NONRATT022748 were correlated with multiple DEGs enriched in cell cycle and division. Moreover, up-regulated TFs Egr1, Cebpd, and Atf4 play crucial roles in regulatory network, and NONRATG020400-Cebpd-Ccl2, NONRATT023505/NONRATT022748-Atf4-Ccna2, and NONRATT022748-Egr1-Id1/Aldoc/Eno2/F3/Serpine1 regulatory pathways were identified in SCs after IL-22 treatment. IL-22 might influence SCs proliferation and apoptosis via regulating lncRNA-TF-gene pathways in SCs. However, more studies are required to confirm these results. [ABSTRACT FROM AUTHOR]

Increasingly arisen environmental constraints may contribute to heritable phenotypic variation including methylation changes, which can help the animals with development, growth and survival. In this study, we assessed the DNA methylation levels in three tissues (gonad, kidney and gill) of half smooth tongue sole under the salinity stress. The methylation-sensitive amplification polymorphism (MSAP) technique was applied to illustrate the regulation of epigenetic mechanism in environmental stimuli. Fish were subjected to 15 salinity treatment for 7 and 60 days, respectively. A total of 11259 fragments were amplified with 8 pairs of selective primers. The levels of methylated DNA in different tissues of females and males without salinity stress were analyzed, which were 32.76% and 47.32% in gonad; 38.13% and 37.69% in kidney; 37.58% and 34.96% in gill, respectively. In addition, the significant difference was observed in gonad between females and males, indicating that discrepant regulation in gonadal development and differentiation may involve sex-related genes. Further analysis showed that total and hemi-methylation were significantly decreased under 15 salinity for 7 days, probably resulting in up-regulating salt-tolerance genes expression to adjust salt changing. With the adjustment for 60 days, total and hemi-methylation prominently went back to its normal levels to obtain equilibrium. Particularly, full methylation levels were steady along with salinity stress to maintain the stability of gene expression. Additionally, the data showed that gonads in females and gills in males were superior in adaptability. As a result, DNA methylation regulates tissue- specific epiloci, and may respond to salinity stress by regulating gene expression to maintain animal survival and activity. [ABSTRACT FROM AUTHOR]

Evidence indicates that neural stem cells (NSCs) can ameliorate cerebral ischemia in animal models. In this study, we investigated the mechanism underlying one of the neuroprotective effects of NSCs: tunneling nanotube (TNT) formation. We addressed whether the control of cell-to-cell communication processes between NSCs and brain microvascular endothelial cells (BMECs) and, particularly, the control of TNT formation could influence the rescue function of stem cells. In an attempt to mimic the cellular microenvironment in vitro, a co-culture system consisting of terminally differentiated BMECs from mice in a distressed state and NSCs was constructed. Additionally, engraftment experiments with infarcted mouse brains revealed that control of TNT formation influenced the effects of stem cell transplantation in vivo. In conclusion, our findings provide the first evidence that TNTs exist between NSCs and BMECs and that regulation of TNT formation alters cell function. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus ( S. aureus) causes a wide variety of infections, which are of major concern worldwide. S. aureus produces multiple virulence factors, resulting in food infection and poisoning. These virulence factors include hyaluronidases, proteases, coagulases, lipases, deoxyribonucleases and enterotoxins. Among the extracellular proteins produced by S. aureus that contribute to pathogenicity, the exotoxins α-hemolysin, staphylococcal enterotoxin A (SEA) and staphylococcal enterotoxin B (SEB) are thought to be of major significance. Totarol, a plant extract, has been revealed to inhibit the proliferation of several pathogens effectively. However, there are no reports on the effects of totarol on the production of α-hemolysin, SEA or SEB secreted by S. aureus. The aim of this study was to evaluate the effects of totarol on these three exotoxins. Hemolysis assay, western blotting and real-time reverse transcriptase-PCR assay were performed to identify the influence of graded subinhibitory concentrations of totarol on the production of α-hemolysin and the two major enterotoxins, SEA and SEB, by S. aureus in a dose-dependent manner. Moreover, an enzyme linked immunosorbent assay showed that the TNF-α production of RAW264.7 cells stimulated by S. aureus supernatants was inhibited by subinhibitory concentrations of totarol. Form the data, we propose that totarol could potentially be used as a promising natural compound in the food and pharmaceutical industries. [ABSTRACT FROM AUTHOR]

The blood-brain barrier (BBB) maintains homeostasis by blocking toxic molecules from the circulation, but drugs are blocked at the same time. When the dose is increased to enhance the drug concentration in the central nervous system, there are side-effects on peripheral organs. In recent years, genetic therapeutic agents and small molecules have been used in various strategies to penetrate the BBB while minimizing the damage to systemic organs. In this review, we describe several representative methods to circumvent or cross the BBB, including chemical and physical strategies. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus is one of the most important pathogens in humans and animals. The formation of biofilm by S. aureus is considered an important mechanism of antimicrobial resistance. Therefore, finding effective drugs against the biofilm produced by S. aureus has been a high priority. Licochalcone A (LAA), a natural plant product, was reported to have antibacterial activities and showed good activity against all 21 tested strains of S. aureus biofilm and planktonic cells. To detect the possible molecular mechanism of LAA against S. aureus biofilm or planktonic cells, Affymetrix GeneChips were used to determine the global comparative transcription of S. aureus biofilm and planktonic cells triggered by treatment with sub-bactericidal and sub-inhibitory concentrations of LAA, respectively. LAA significantly altered (greater than a 2- or less than −2-fold change) the expression of 693 genes in planktonic cells and 817 genes in biofilm. The levels of genes encoding autolysis-associated proteins, cell wall proteins, pathogenic factors, protein synthesis genes, and enzymes involved in capsule synthesis were significantly altered in LAA-treated S. aureus. Furthermore, some differences observed in the microarray analysis were verified by real-time RT-PCR. To our knowledge, this is the first observation of phenotype and expression profiles of S. aureus biofilm and planktonic cells in response to LAA treatment. [ABSTRACT FROM AUTHOR]

Ozonesondes are widely used to obtain ozone concentration profiles from the surface to the upper atmosphere. A kind of double-cell ozonesonde has been developed at the Institute of Atmospheric Physics (IAP), Chinese Academy of Sciences (named the 'IAP ozonesonde') based on previous experience over the past 20 years of developing the singlecell GPSO3 ozonesonde. The IAP ozonesonde is of the Electrochemical Concentration Cell (ECC) type. A detailed description of the IAP ozonesonde is firstly provided in the present paper, followed by a presentation of results from a series of launches carried out to evaluate its performance. The analysis involved comparing its observations with measurements from the GPSO3 and ECC ozonesondes (Model type ENSCI-Z) as well as a Brewer spectrophotometer. The results showed that the IAP ozonesonde is a vast improvement over the GPSO3 ozonesonde, able to capture vertical ozone structures very well and in good agreement with ECC ozonesonde measurements. The average difference in the ozone partial pressure between the IAP and ECC ozonesondes was 0.3 mPa from the surface to 2.5 km, close to zero from 2.5 to 9 km and generally less than 1 mPa for layers higher than 9 km. The apparent deviation is likely caused by a decreasing pump flow rate in the IAP ozonesonde which needs further improvement. The total ozone amounts measured by the IAP ozonesonde profiles were highly comparable with the Brewer data with a relative difference of 6%. The development of the IAP ozonesonde and its strong performance will surely accelerate the process of conventional observations of ozone profiles over China in the near future as well as provide more data for ozone research in general. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is the most prevalent demyelinating disease and the principal cause of neurological disability in young adults. Recent microarray gene expression profiling studies have identified several genetic variants contributing to the complex pathogenesis of MS, however, expressional and functional studies are still required to further understand its molecular mechanism. The present study aimed to analyze the molecular mechanism of MS using microarray analysis combined with bioinformatics techniques. We downloaded the gene expression profile of MS from Gene Expression Omnibus (GEO) and analysed the microarray data using the differentially coexpressed genes (DCGs) and links package in R and Database for Annotation, Visualization and Integrated Discovery. The regulatory impact factor (RIF) algorithm was used to measure the impact factor of transcription factor. A total of 1,297 DCGs between MS patients and healthy controls were identified. Functional annotation indicated that these DCGs were associated with immune and neurological functions. Furthermore, the RIF result suggested that IKZF1, BACH1, CEBPB, EGR1, FOS may play central regulatory roles in controlling gene expression in the pathogenesis of MS. Our findings confirm the presence of multiple molecular alterations in MS and indicate the possibility for identifying prognostic factors associated with MS pathogenesis. [ABSTRACT FROM AUTHOR]

The excretory-secretory products (ESP) released by muscle stage of Trichinella spiralis have been suggested to be involved in nurse cell formation. However, the molecular mechanisms by which ESP modulate nurse cell formation remain unclear. In the present study, the ability of ESP of muscle larvae of T. spiralis (ML-ESP) to influence the proliferation and differentiation of murine myoblasts and the mechanisms were evaluated in vitro using C2C12 myoblast cell line, which were incubated for various times under grow or differentiation culture medium containing various concentrations of ML-ESP. The results indicated that ML-ESP promoted myoblast proliferation in a dose-dependent manner and increased the expression of the cell-cycle regulator cyclin D1 as well as that of proliferating cell nuclear antigen (PCNA). Conversely, ML-ESP inhibited the differentiation of these cells, which was evidenced by a reduction in the levels of MHC and MRFs expression (MyoD and myogenin) as well as that of p21. In addition, ML-ESP also inhibited the phosphorylation of p38 MAPK in differentiating C2C12 myoblast. Taken together, these results imply that certain critical mediators contained in ML-ESP inhibit myogenesis through enhancing skeletal myoblasts proliferation and down-regulating the expression of MRFs as well as involving p38 MAPK signalling pathway, which provides insight into the mechanisms utilised by T. spiralis to interfere normal wound repair in infected muscle cells and affect nurse cell formation. [ABSTRACT FROM AUTHOR]

Trichinella spiralis is a zoonotic nematode and food borne parasite and infection with T. spiralis leads to suppression of the host immune response and other immunopathologies. The excretory/secretory (ES) products of T. spiralis play important roles in the process of immunomodulation. However, the mechanisms and related molecules are unknown. Macrophages, a target for immunomodulation by the helminth parasite, play a critical role in initiating and modulating the host immune response to parasite infection. In this study, we examined the effect of ES products from different stages of T. spiralis on modulating J774A.1 macrophage activities . ES products from different stages of T. spiralis reduced the capacity of macrophages to express pro-inflammatory cytokines (tumor necrosis factor α, interleukin-1β , interleukin-6 , and interleukin-12) in response to lipopolysaccharide (LPS) challenge. However, only ES products from 3-day-old adult worms and 5-day-old adult worms/new-born larvae significantly inhibited inducible nitric oxide synthase gene expression in LPS-induced macrophages. In addition, ES products alone boosted the expression of anti-inflammatory cytokines interleukin-10 and transforming growth factor-β and effector molecule arginase 1 in J774A.1 macrophages. Signal transduction studies showed that ES products significantly inhibited nuclear factor-κB translocation into the nucleus and the phosphorylation of both extracellular signal-regulated protein kinase 1/2 and p38 mitogen-activated protein kinase in LPS-stimulated J774A.1 macrophages. These results suggest that ES products regulate host immune response at the macrophage level through inhibition of pro-inflammatory cytokines production and induction of macrophage toward the alternative phenotype, which maybe important for worm survival and host health. [ABSTRACT FROM AUTHOR]

Mycobacterium tuberculosis ( M. tuberculosis) remains one of the world's most prevalent and serious pathogens, and multiple resistant strains are increasingly widespread. The recent emergence of multidrug-resistant and extensively drug-resistant (XDR-TB) strains has increased the importance of searching for alternative targets to develop new antimycobacterial drugs. Plumbagin (PL), a natural plant product, has been reported to have potential antimicrobial activity against M. tuberculosis, but the response mechanisms of M. tuberculosis to PL are still poorly understood. In this study, we used a commercial oligonucleotide microarray to determine the overall transcriptional response of M. tuberculosis H37Rv triggered by exposure to subinhibitory concentrations of PL. A total of 274 genes were found to be differentially regulated by PL. Of these, 103 genes were upregulated, and 171 genes were downregulated. A number of important genes were significantly regulated that are involved in various pathways, such as chaperonins, PE/PPE multigene families, and genes involved in the cell envelope, virulence, and 50S ribosomes. To our knowledge, this genome-wide transcriptomics approach has produced the first insights into the response of M. tuberculosis to a PL challenge. These results will pave the way for exploring the mechanisms of PL action against M. tuberculosis. [ABSTRACT FROM AUTHOR]

Fumonisin B1 (FB1) is one of the important mycotoxins posing health risks in the area of food safety. A sensitive fluorescence ratio immunoassay has been established for FB1 based on the growth of monodispersed 2-D MnO2 nanosheet on an individual gold nanoparticle (AuNP@MnO2). FB1 competed with the coated FB1-BSA to bind the FB1 monoclonal antibody. After a washing step, alkaline phosphatase-labeled goat anti-mouse IgG (ALP-IgG) with high catalytic activity was combined with FB1 monoclonal antibody. ALP reacts with ascorbic acid 2-phosphate (AAP) to produce ascorbic acid (AA), which decomposes AuNP@MnO2 to dehydroascorbic acid (DHAA). O-Phenylenediamine dihydrochloride (OPD) is oxidized to yellow-fluorescent substrate of 2,3-diaminophenazine (DAP) (excitation, 423 nm; emission, 570 nm) by AuNP@MnO2. Meanwhile, OPD can also be reduced to blue fluorescent substrate of OPDred (excitation, 350 nm; emission, 430 nm) by DHAA. The content of FB1 can be determined by fluorescence ratio of blue/yellow. The limit of detection (LOD) of the fluorescence ratio immunoassay for FB1 was 0.06 ng mL−1, and the linear range was from 0.25 to 60.00 ng mL−1. The effectiveness of the assay was verified in real maize samples, and satisfactory recoveries were attained. The correlation coefficient of these results between the fluorescence ratio immunoassay and commercial ELISA kit was 0.9999. This method provides a sensitive and selective tool for the detection of FB1 in maize samples. [ABSTRACT FROM AUTHOR]