Lavender improves sleep through olfactory perception and GABAergic neurons of the central amygdala.

ETHNOPHARMACOLOGICAL RELEVANCE: The use of lavender as sleep aid or hypnotic agent can be traced back as early as ancient Romans and Greeks. Yet, objective experimental data on whether and how lavender enhances sleep duration or/and sleep quality remain lacking. AIM OF THE STUDY: We aimed to characterize the sleep-wake regulating effects of lavender in the mouse and to demonstrate the brain targets and neural circuits involved. MATERIALS AND METHODS: A self-made precise odor delivery system combined with chronic polysomnographic recordings was employed to assess the sleep-wake effects of inhalation with lavender essential oil (LEO, extracted from lavender) and its different constituents during the light and dark phases in free-moving C57BL/6J mice. Neuroviral labeling, in situ hybridization and pharmacogenetics were combined to identify the neural circuits and targets involved. Finally, an insomniac model of DL-4-Chlorophenylalanine (PCPA)-treated mice was established to examine the sleep-inducing potential of LEO. RESULTS: We found that inhalation of LEO with a concentration at 25.0% during the light (inactive) phase significantly shortened the latency to non-rapid eye movement (NREM) sleep, increased the total amount of NREM sleep at the expense of wakefulness (W), and enhanced cortical EEG slow wave activities, notably delta power spectra density. We further identified linalool, d-limonene, 1,8-cineole, linalyl acetate and terpinene-4-ol as the major effective sleep-promoting monomer components. Importantly, we found that LEO no longer produced any of the above sleep-promoting effect following either nasal injection of zinc sulfate which interrupts the olfactory pathway, or pharmacogenetics silencing of central amygdala GABAergic neurons. Finally, LEO reestablished NREM sleep with short latency in PCPA-treated insomniac mice, effects comparable with those induced by a potent sedative diazepam. CONCLUSIONS: We have characterized the quantitative and qualitative sleep-promoting effects of LEO and its effective components via the olfactory pathway and central amygdala GABA neuronal targets. The hypnotic property of LEO is reinforced by its ability to restore sleep in insomnia. Our study thus establishes a neurobiological basis for aromatherapy of sleep disorders using lavender.

The Sec pathway gene yidC regulates the virulence of mesophilic Aeromonassalmonicida.

Aeromonas salmonicida is a common pathogenic bacterial species found in both freshwater and marine fish, leading to significant economic losses in the aquaculture industry. YidC is an accessory to SecYEG and is essential for the SecYEG transporter to insert into the bacterial membrane. However, the roles of the yidC gene on the host immune response remain unclear. Here, we compared the pathogenicity of yidC gene-deleted (ΔyidC) strain and wild-type (SRW-OG1) strain of mesophilic A. salmonicida to Orange-spotted grouper (Epinephelus coioides), and explored the impacts of yidC gene on the immune response of E. coioides to mesophilic A. salmonicida infection by using Red/ET recombineering. In this study, the E. coioides in the Secondary infected group had a 53.9 % higher survival rate than those in the Primary infected group. In addition, the adhesion ability of ΔyidC strain decreased by about 83.36 % compared with that of the wild-type (SRW-OG1) strain. Further comparison of the biological phenotype of SRW-OG1 and ΔyidC revealed that this yidC gene could regulate the expression of genes related to iron metabolism and have no effect on bacterial growth under the limited iron concentration. In the low concentration of Fe3+ and Fe2+ environment, SRW-OG1 can obtain iron ions by regulating yidC. Based on the above results, yidC gene contributed to the pathogenicity of mesophilic A. salmonicida to E. coioides, deletion of yidC gene promoted the inflammation and immune response of E. coioides to mesophilic A. salmonicida infection.

Bio-organic fertilizer facilitated phytoremediation of heavy metal(loid)s-contaminated saline soil by mediating the plant-soil-rhizomicrobiota interactions.

Bio-organic fertilizer (BOF) was effective to promote the phytoremediation efficiency of heavy metal(loid)s-contaminated saline soil (HCSS) by improving rhizosphere soil properties, especially microbiome. However, there existed unclear impacts of BOF on plant metabolome and plant-driven manipulation on rhizosphere soil microbiota in HCSS, which were pivotal contributors to stress defense of plants trapped in adverse conditions. Here, a pot experiment was conducted to explore the mechanisms of BOF in improving alfalfa (Medicago sativa)-performing phytoremediation of HCSS. BOF application significantly increased the biomass (150.87-401.58 %) to support the augments of accumulation regarding heavy metal(loid)s (87.50 %-410.54 %) and salts (38.27 %-271.04 %) in alfalfa. BOF promoted nutrients and aggregates stability but declined pH of rhizosphere soil, accompanied by the boosts of rhizomicrobiota including increased activity, reshaped community structure, enriched plant growth promoting rhizobacteria (Blastococcus, Modestobacter, Actinophytocola, Bacillus, and Streptomyces), strengthened mycorrhizal symbiosis (Leohumicola, Funneliformis, and unclassified_f_Ceratobasidiaceae), optimized co-occurrence networks, and beneficial shift of keystones. The conjoint analysis of plant metabolome and physiological indices confirmed that BOF reprogrammed the metabolic processes (synthesis, catabolism, and long-distance transport of amino acid, lipid, carbohydrate, phytohormone, stress-resistant secondary metabolites, etc) and physiological functions (energy supply, photosynthesis, plant immunity, nutrients assimilation, etc) that are associated intimately. The consortium of root metabolome, soil metabolome, and soil microbiome revealed that BOF facilitated the exudation of metabolites correlated with rhizomicrobiota (structure, biomarker, and keystone) and rhizosphere oxidative status, e.g., fatty acyls, phenols, coumarins, phenylpropanoids, highlighting the plant-driven regulation on rhizosphere soil microbes and environment. By compiling various results and omics data, it was concluded that BOF favored the adaptation and phytoremediation efficiency of alfalfa by mediating the plant-soil-rhizomicrobiota interactions. The results would deepen understanding of the mechanisms by which BOF improved phytoremediation of HCSS, and provide theoretical guidance to soil amelioration and BOF application.

Transcriptomic analysis of Vibrio alginolyticus challenged by Rhizoma coptidis reveals mechanisms of virulence genes.

Rhizoma coptidis, a Chinese herbal medicine widely used to treat various bacterial infections, has the potential to develop antibiotic substitutes to overcome the drug resistance of Vibrio alginolyticus. To study the inhibitory effect of R. coptidis on V. alginolyticus, we sequenced the transcriptomes of three groups of samples of wild-type V. alginolyticus (CK) and V. alginolyticus, which were stressed by 5 mg/mL R. coptidis for 2 h (RC_2 h) and 4 h (RC_4 h). CK was compared with RC_2 h and RC_4 h, respectively, and a total of 1565 differentially expressed genes (DEGs) (988 up-regulated and 577 down-regulated) and 1737 DEGs (1152 up-regulated and 585 down-regulated) were identified. Comparing RC_2 h with RC_4 h, 156 DEGs (114 up-regulated and 42 down-regulated) were identified. The ability of biofilm formation and motility of V. alginolyticus altered upon with different concentrations of R. coptidis. Interestingly, relative expression patterns of virulence genes appeared statistically significantly varied, upon different concentrations of R. coptidis extract. DEGs were annotated to the Gene Ontology (GO) database for function enrichment analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, the results showed that the main enriched pathways, was those related to the virulence of V. alginolyticus. This study provides a new perspective for understanding the complex pathogenic mechanism of V. alginolyticus. R. coptidis could potnetially be used as alternative or complimnetary to antibiotics to treat infections after further research.

Identification the Low Oxidative Stress Subtype of Periodontitis.

OBJECTIVE: The aim of this research was to identify the low oxidative stress-related genes expression (L-OS) subtype in patients with periodontitis. METHODS: Microarray data (MA) were retrieved from the Gene Expression Omnibus database. The different oxidative stress (OS) subtypes of periodontitis were identified by K-means clustering analysis and gene set variation analysis (GSVA). Differentially expressed genes (DEGs) (|Log fold change (FC)| >1, q < 0.05) amongst the OS subtypes and healthy controls (HCs) were identified by Limma R package. The genomic feature of L-OS subtype and corresponding medicines were evaluated and visualised with Drug-Gene Interaction Database and cytoscape-v3.7.2 software (Pearson correlation coefficient > 0.4). Finally, the LASSO-Logistic regression model was adopted to evaluate and predict patients' OS phenotype in routine clinical practice. RESULTS: The 241 periodontitis samples and 69 HCs were included. Thirty-three DEGs between the L-OS and high oxidative stress-related genes expression (H-OS) subtypes and 96 DEGs, including 8 transcription factors, between L-OS subtype and HCs were identified, respectively. Then, the network of TFs-Genes-Drugs was constructed to determine genomic feature of L-OS subtype. Finally, a 4-gene signature formula and the cutoff value were identified by ML with LASSO model to predict patients' classification. CONCLUSIONS: For the first time, we identified L-OS subtype of periodontitis and evaluated its genomic feature with MA.

4D Printed Shape-Memory Elastomer for Thermally Programmable Soft Actuators.

Polymeric shape-memory elastomers can recover to a permeant shape from any programmed deformation under external stimuli. They are mostly cross-linked polymeric materials and can be shaped by three-dimensional (3D) printing. However, 3D printed shape-memory polymers so far only exhibit elasticity above their transition temperature, which results in their programmed shape being inelastic or brittle at lower temperatures. To date, 3D printed shape-memory elastomers with elasticity both below and above their transition temperature remain an elusive goal, which limits the application of shape-memory materials as elastic materials at low temperatures. In this paper, we printed, for the first time, a custom-developed shape-memory elastomer based on polyethylene glycol using digital light processing, which possesses elasticity and stretchability in a wide temperature range, below and above the transition temperature. Young's modulus in these two states can vary significantly, with a difference of up to 2 orders of magnitude. This marked difference in Young's modulus imparts excellent shape-memory properties to the material. The difference in Young's modulus at different temperatures allows for the programming of the pneumatic actuators by heating and softening specific areas. Consequently, a single actuator can exhibit distinct movement modes based on the programming process it undergoes.

Label-Free Sequence-Specific Visualization of LAMP Amplified Salmonella via DNA Machine Produces G-Quadruplex DNAzyme.

Salmonella is one of four key global causes of diarrhea, and in humans, it is generally contracted through the consumption of contaminated food. It is necessary to develop an accurate, simple, and rapid method to monitor Salmonella in the early phase. Herein, we developed a sequence-specific visualization method based on loop-mediated isothermal amplification (LAMP) for the detection of Salmonella in milk. With restriction endonuclease and nicking endonuclease, amplicons were produced into single-stranded triggers, which further promoted the generation of a G-quadruplex by a DNA machine. The G-quadruplex DNAzyme possesses peroxidase-like activity and catalyzes the color development of 2,2'-azino-di-(3-ethylbenzthiazoline sulfonic acid) (ABTS) as the readouts. The feasibility for real samples analysis was also confirmed with Salmonella spiked milk, and the sensitivity was 800 CFU/mL when observed with the naked eye. Using this method, the detection of Salmonella in milk can be completed within 1.5 h. Without the involvement of any sophisticated instrument, this specific colorimetric method can be a useful tool in resource-limited areas.

Genetic analysis of Vibrio alginolyticus challenged by Fructus schisandrae reveals the mechanism of virulence genes.

Due to the abusive use of antibiotics, bacterial resistance has become a global problem and poses severe threats to aquaculture. The drug-resistant diseases caused by Vibrio alginolyticus have caused significant economic losses to cultured marine fish. Fructus schisandrae is used to treat inflammatory diseases in China and Japan. There have been no reports of bacterial molecular mechanisms associated with F. schisandrae stress. In this study, the inhibiting effect of F. schisandrae on the growth of V. alginolyticus was detected to understand response mechanisms at the molecular level. The antibacterial tests were analyzed via next-generation deep sequencing technology (RNA sequencing, RNA-seq). Wild V. alginolyticus (CK) was compared with V. alginolyticus, F. schisandrae incubated for 2 h, and V. alginolyticus, F. schisandrae incubated for 4 h. Our results revealed that there were 582 genes (236 upregulated and 346 downregulated) and 1068 genes (376 upregulated and 692 downregulated), respectively. Differentially expressed genes (DEGs) were involved in the following functional categories: metabolic process, single-organism process, catalytic activity, cellular process, binding, membrane, cell part, cell, and localization. FS_2 h was compared with FS_4 h, and 21 genes (14 upregulated and 7 downregulated) were obtained. The RNA-seq results were validated by detecting the expression levels of 13 genes using quantitative real-time polymerase chain reaction (qRT-PCR). The qRT-PCR results matched those of the sequencing, which reinforced the reliability of the RNA-seq. The results revealed the transcriptional response of V. alginolyticus to F. schisandrae, which will provide new ideas for studying V. alginolyticus' complex virulence molecular mechanism and the possibility of developing Schisandra to prevent and treat drug-resistant diseases.

Bio-organic fertilizer promoted phytoremediation using native plant leymus chinensis in heavy Metal(loid)s contaminated saline soil.

Heavy metal(loid)s (HMs) contaminated saline soil appeared around the world, however, remediation regarding these collected from field conditions remains unknown. Native plants cultivation and bio-organic fertilizer (BOF) application were two efficient tools for soil amelioration. Herein, a pot experiment was conducted to examine the feasibility of a native plant (Leymus chinensis) for phytoremediation, and investigate the impacts of lignite based bio-organic fertilizer (LBOF) and manure based bio-organic fertilizer (MBOF) on phytoremediation of the soil contaminated by Pb, Cd, As, Zn, Cu, Ca2+, and SO42-. The results demonstrated the effectiveness of L. chinensis and highlighted the positive impacts of BOF according to the improved plant growth, HMs phytostabilization, salt removal, and soil properties. LBOF and MBOF changed soil microbiome to assist phytoremediation in addition to physiological modulation. Having enhanced fungal and bacterial richness respectively, LBOF and MBOF recruited various plant growth promoting rhizobacteria with different functions, and shifted microbial co-occurrence networks and keystone taxa towards these different but beneficial forms. Structural equation models comprehensively reveled the strategy discrepancy of LBOF and MBOF to regulate the plant biomass, HMs uptake, and soil salt. In summary, L. chinensis coupled with BOF, especially LBOF, was a effective strategy to remediate HMs contaminated saline soil.

Fabrication of Multi-Material Pneumatic Actuators and Microactuators Using Stereolithography.

Pneumatic actuators are of great interest for device miniaturization, microactuators, soft robots, biomedical engineering, and complex control systems. Recently, multi-material actuators have become of high interest to researchers due to their comprehensive range of suitable applications. Three-dimensional (3D) printing of multi-material pneumatic actuators would be the ideal way to fabricate customized actuators, but so far, this is mostly limited to deposition-based methodologies, such as fused deposition modeling (FDM) or Polyjetting. Vat-based stereolithography is one of the most relevant high-resolution 3D printing methods but is only rarely utilized in the multi-material 3D printing of materials. This study demonstrated multi-material stereolithography using combinations of materials with different Young's moduli, i.e., 0.5 MPa and 1.1 GPa, for manufacturing pneumatic actuators and microactuators with a resolution as small as 200 µm. These multi-material actuators have advantages over single-material actuators in terms of their deformation controllability and ease of assembly.

Mechanisms Underlying the Virulence Regulation of Vibrio alginolyticus ND-01 pstS and pstB with a Transcriptomic Analysis.

Vibrio alginolyticus is a common opportunistic pathogen of fish, shrimp, and shellfish, and many diseases it causes can result in severe economic losses in the aquaculture industry. Causing host disease was confirmed by several virulence factors of V. alginolyticus. To date, there have been no reports on the effect of the pstS gene on its virulence regulation of V. alginolyticus. The virulence mechanism of target genes regulating V. alginolyticus is worthy of further study. Previous studies found that Fructus schisandrae (30 mg/mL) inhibited the growth of V. alginolyticus ND-01 (OD600 = 0.5) for 4 h, while the expressions of pstS and pstB were significantly affected by F. schisandrae stress. So, we speculated that pstS and pstB might be the virulence genes of V. alginolyticus, which were stably silenced by RNAi to construct the silencing strains pstS-RNAi and pstB-RNAi, respectively. After the expression of pstS or pstB gene was inhibited, the adhesion capacity and biofilm formation of V. alginolyticus were significantly down-regulated. The chemotaxis and biofilm formation ability of pstS-RNAi was reduced by 33.33% and 68.13% compared with the wild-type strain, respectively. Sequence alignment and homology analysis showed that pstS was highly conserved, which suggested that pstS played a vital role in the secretion system of V. alginolyticus. The pstS-RNAi with the highest silencing efficiency was selected for transcriptome sequencing. The Differentially Expressed Genes (DEGs) and GO terms were mapped to the reference genome of V. alginolyticus, including 1055 up-regulated genes and 1134 down-regulated genes. The functions of the DEGs were analyzed by GO and categorized into different enriched functional groups, such as ribosome synthesis, organelles, biosynthesis, pathogenesis, and secretion. These DEGs were then mapped to the reference KEGG pathways of V. alginolyticus and enriched in commonalities in the metabolic, ribosomal, and bacterial secretion pathways. Therefore, pstS and pstB could regulate the bacterial virulence of V. alginolyticus by affecting its adhesion, biofilm formation ability, and motility. Understanding the relationship between the expressions of pstS and pstB with bacterial virulence could provide new perspectives to prevent bacterial diseases.

Rapid Eye Movement Sleep during Early Life: A Comprehensive Narrative Review.

The ontogenetic sleep hypothesis suggested that rapid eye movement (REM) sleep is ontogenetically primitive. Namely, REM sleep plays an imperative role in the maturation of the central nervous system. In coincidence with a rapidly developing brain during the early period of life, a remarkably large amount of REM sleep has been identified in numerous behavioral and polysomnographic studies across species. The abundant REM sleep appears to serve to optimize a cerebral state suitable for homeostasis and inherent neuronal activities favorable to brain maturation, ranging from neuronal differentiation, migration, and myelination to synaptic formation and elimination. Progressively more studies in Mammalia have provided the underlying mechanisms involved in some REM sleep-related disorders (e.g., narcolepsy, autism, attention deficit hyperactivity disorder (ADHD)). We summarize the remarkable alterations of polysomnographic, behavioral, and physiological characteristics in humans and Mammalia. Through a comprehensive review, we offer a hybrid of animal and human findings, demonstrating that early-life REM sleep disturbances constitute a common feature of many neurodevelopmental disorders. Our review may assist and promote investigations of the underlying mechanisms, functions, and neurodevelopmental diseases involved in REM sleep during early life.

Enhanced Hemolytic Activity of Mesophilic Aeromonas salmonicida SRW-OG1 Is Brought about by Elevated Temperatures.

Aeromonas salmonicida is a well-known cold-water pathogenic bacterium. Previously, we reported the first isolation of pathogenic A. salmonicida from diseased Epinephelus coioides, a kind of warm-water fish, and it was proved to be a putative mesophilic strain with potent pathogenicity to humans. In order to investigate the mechanisms underlying mesophilic growth ability and virulence, the transcriptome of A. salmonicida SRW-OG1 at 18, 28, and 37 °C was analyzed. The transcriptome of A. salmonicida SRW-OG1 at different temperatures showed a clear separation boundary, which might provide valuable information for the temperature adaptation and virulence regulation of A. salmonicida SRW-OG1. Interestingly, aerA and hlyA, the hemolytic genes encoding aerolysin and hemolysin, were found to be significantly up-regulated at 28 and 37 °C. Since aerolysin and hemolysin are the most well-known and -characterized virulence factors of pathogenic Aeromonas strains, the induction of aerA and hlyA was associated with the mesophilic virulence. Further study proved that the extracellular products (ECPs) purchased from A. salmonicida SRW-OG1 cultured at 28 and 37 °C showed elevated hemolytic activity and virulence than those at 18 °C. Moreover, the silence of aerA and hlyA led to significantly decreased hemolysis and virulence. Taken together, our results revealed that the mesophilic virulence of A. salmonicida SRW-OG1 might be due to the enhanced expression of aerA and hlyA induced by elevated temperatures.

The temperature-dependent expression of type II secretion system controls extracellular product secretion and virulence in mesophilic Aeromonas salmonida SRW-OG1.

Aeromonas salmonicida is a typical cold water bacterial pathogen that causes furunculosis in many freshwater and marine fish species worldwide. In our previous study, the pathogenic A. salmonicida (SRW-OG1) was isolated from a warm water fish, Epinephelus coioides was genomics and transcriptomics analyzed. Type II secretion system was found in the genome of A. salmonicida SRW-OG1, while the expressions of tatA, tatB, and tatC were significantly affected by temperature stress. Also, sequence alignment analysis, homology analysis and protein secondary structure function analysis showed that tatA, tatB, and tatC were highly conservative, indicating their biological significance. In this study, by constructing the mutants of tatA, tatB, and tatC, we investigated the mechanisms underlying temperature-dependent virulence regulation in mesophilic A. salmonida SRW-OG1. According to our results, tatA, tatB, and tatC mutants presented a distinct reduction in adhesion, hemolysis, biofilm formation and motility. Compared to wild-type strain, inhibition of the expression of tatA, tatB, and tatC resulted in a decrease in biofilm formation by about 23.66%, 19.63% and 40.13%, and a decrease in adhesion ability by approximately 77.69%, 80.41% and 62.14% compared with that of the wild-type strain. Furthermore, tatA, tatB, and tatC mutants also showed evidently reduced extracellular enzymatic activities, including amylase, protease, lipase, hemolysis and lecithinase. The genes affecting amylase, protease, lipase, hemolysis, and lecithinase of A. salmonicida SRW-OG1 were identified as cyoE, ahhh1, lipA, lipB, pulA, HED66_RS01350, HED66_RS19960, aspA, fabD, and gpsA, which were notably affected by temperature stress and mutant of tatA, tatB, and tatC. All above, tatA, tatB and tatC regulate the virulence of A. salmonicida SRW-OG1 by affecting biofilm formation, adhesion, and enzymatic activity of extracellular products, and are simultaneously engaged in temperature-dependent pathogenicity.

Stereotaxic atlas of the infant rat brain at postnatal days 7-13.

Recently, researchers have paid progressively more attention to the study of neural development in infant rats. However, due to the lack of complete intracerebral localization information, such as clear nuclear cluster boundaries, identified main brain structures, and reliable stereotaxic coordinates, it is difficult and restricted to apply technical neuroscience to infant rat's brain. The present study was undertaken to refine the atlas of infant rats. As such, we established a stereotaxic atlas of the infant rat's brain at postnatal days 7-13. Furthermore, dye calibration surgery was performed in P7-P13 infant rats by injecting Methylene blue, and sections were incubated in Nissl solutions. From the panoramic images of the brain sections, atlases were made. Our article has provided the appearance and measurements of P7-P13 Sprague-Dawley rat pups. Whereas the atlas contains a series of about 530 coronal brain section images from olfactory bulbs to the brainstem, a list of abbreviations of the main brain structures, and reliable stereotaxic coordinates, which were demonstrated by vertical and oblique injections with fluorescent dye DiI. The present findings demonstrated that our study of P7-P13 atlases has reasonable nucleus boundaries and accurate and good repeatability of stereotaxic coordinates, which can make up for the shortage of postnatal rat brain atlas currently in the field.

Decarboxylative Addition of Propiolic Acids with Indoles to Synthesize Bis(indolyl)methane Derivatives with a Pd(II)/LA Catalyst.

Exploring new protocols for efficient organic synthesis is crucial for pharmaceutical developments. The present work introduces a Pd(II)/LA-catalyzed (LA: Lewis acid) decarboxylative addition reaction for the synthesis of bis(indolyl)methane derivatives. The presence of Lewis acid such as Sc(OTf)3 triggered Pd(II)-catalyzed decarboxylative addition of propiolic acids with indoles to offer the bis(indolyl)methane derivatives in moderate to good yields, whereas neither Pd(II) nor Lewis acid alone was active for this synthesis. The catalytic efficiency of Pd(OAc)2 was highly dependent on the Lewis acidity of the added Lewis acid, that is, a stronger Lewis acid provided a higher yield of the bis(indolyl)methane derivatives. Meanwhile, this Pd(II)/LA-catalyzed decarboxylative addition reaction showed good tolerance toward versatile electron-rich or -deficient substituents on the indole skeleton and on the benzyl ring of propiolic acids. The studies on the in situ 1H NMR kinetics of this Pd(II)/Sc(III) catalysis disclosed the formation of a transient vinyl-Pd(II)/Sc(III) intermediate generated by the pyrrole addition to the alkynyl-Pd(II)/Sc(III) species after decarboxylation, which was scarcely observed before.

One-step treatment of periodontitis based on a core-shell micelle-in-nanofiber membrane with time-programmed drug release.

As a chronic inflammatory disease, periodontitis is responsible for irreversible soft tissue damage and severe alveolar bone resorption. However, curative effects of current therapies are largely confined by the difficulty to simultaneously achieve anti-inflammation and bone regeneration. Also, the dynamic environment in oral cavity easily causes the drugs swallowed or rinsed away by saliva. We report here a one-step treatment based on a core-shell nanofiber membrane fabricated by coaxial electrospinning. Polymeric micelles containing SP600125 were distributed in the shell, while BMP-2 was incorporated in the core. After crosslinking, the nanofiber membrane displayed a prolonged degradation and release period up to 4 weeks. The release of SP600125 was detected at beginning, whereas BMP-2 was not released until day 12. Such a time-programmed release behavior was proved desirable for suppressing the expression of pro-inflammatory factors and enhancing the osteogenic induction in vitro. Further in vivo investigation confirmed that, by simply covering the periodontitis site with our nanofiber membrane, alveolar destruction was largely avoided and bone defects recovered within 2 month. Taken together, we believe that the use of our membrane with sequential release of SP600125 and BMP-2 may become a convenient and highly comprehensive therapy for periodontitis.

Chemical behaviors and toxic effects of ametryn during the UV/chlorine process.

Ametryn (AMT), one of the most widely used herbicides in agriculture, has been frequently detected as a micropollutant in many aquatic environments. AMT residue not only pollutes water but also acts as a precursor for the production of disinfection by-products (DBPs). This study systematically investigated the fate of AMT during the UV/chlorine process. It was observed that the combination of UV irradiation and chlorination degraded AMT synergistically. The results of the radical quenching experiments suggested that AMT degradation by the UV/chlorine process involved the participation of UV photolysis, hydroxyl radical (OH) reactions, and reactive chlorine species (RCS) reactions, which accounted for 45.4%, 36.4%, and 14.5% of the degradation, respectively. Moreover, we found that Cl- 2 was an important reactive radical for AMT degradation. The chlorine dose, pH, coexisting anions (Cl- and HCO3-), and natural organic matter (NOM) were found to affect AMT degradation during the UV/chlorine process. Nineteen predominant intermediates/products of AMT degradation during UV/chlorine process were identified, including atrazine. Moreover, the corresponding transformation pathways were proposed, including electron transfer, bond cleavage (C-S, C-N), radical (OH, Cl and Cl- 2) reactions, and subsequent hydroxylation. The toxicity tests with Vibrio fischeri on AMT degradation suggested that more DBPs were generated by UV/chlorine-treated AMT, which possessed higher acute toxicity than AMT did. Although the UV/chlorine process evidently promoted the AMT degradation, optimization of process parameters may reduce the DBP production and merits further investigation.

cheA, cheB, cheR, cheV, and cheY Are Involved in Regulating the Adhesion of Vibrio harveyi.

Diseases caused by Vibrio harveyi lead to severe economic losses in the aquaculture industry. Adhesion is an important disease-causing factor observed in bacteria with chemotactic activity. In our study, we measured the adhesion of V. harveyi by subjecting the bacteria to stress using Cu2+, Pb2+, Hg2+, and Zn2+. The genes responsible for chemotaxis (cheA, cheB, cheR, cheV, and cheY), which are also crucial for adhesion, were identified and silenced via RNAi. We observed that a decrease in chemotactic gene expression reduced the ability of the organism to demonstrate adhesion, motility, chemotaxis, and biofilm formation. Upon comparing the cheA-RNAi bacteria to the wild-type strain, we observed that the transcriptome of V. harveyi was significantly altered. Additionally, the expression of key genes and the adhesion ability were affected by the pH (pH of 5, 6, 7, 8, and 9), salinity (NaCl at concentrations of 0.8, 1.5, 2.5, 3.5, or 4.5%), and temperature (4, 15, 28, 37, and 44°C) of the medium. Based on these results, the following conclusions were made: (1) The chemotactic genes cheA, cheB, cheR, cheV, and cheY may regulate the adhesion ability of V. harveyi by affecting bacterial motility, and participate in the regulation of adhesion at different temperatures, salinities, and pH values; (2) stable silencing of cheA could alter the transcriptional landscape of V. harveyi and regulate the expression of genes associated with its adhesion mechanisms.

A Novel Continuously Recording Approach for Unraveling Ontogenetic Development of Sleep-Wake Cycle in Rats.

Sleep-wake development in postnatal rodent life could reflect the brain maturational stages. As the altricial rodents, rats are born in a very undeveloped state. Continuous sleep recording is necessary to study the sleep-wake cycle profiles. However, it is difficult to realize in infant rats since they rely on periodic feeding before weaning and constant warming and appropriate EEG electrodes. We developed a new approach including two types of EEG electrodes and milk-feeding system and temperature-controlled incubator to make continuously polysomnographic (PSG) recording possible. The results showed that there was no evident difference in weight gaining and behaviors between pups fed through the milk-feeding system and warmed with temperature-controlled incubator and those kept with their dam. Evolutional profiles of EEG and electromyogram (EMG) activities across sleep-wake states were achieved perfectly during dark and light period from postnatal day (P) 11 to P75 rats. The ontogenetic features of sleep-wake states displayed that the proportion of rapid eye movement (REM) was 57.0 ± 2.4% and 59.7 ± 1.7% and non-REM (NREM) sleep was 5.2 ± 0.8% and 4.9 ± 0.5% respectively, in dark and light phase at P11, and then REM sleep progressively decreased and NREM sleep increased with age. At P75, REM sleep in dark and light phase respectively, reduced to 6.3 ± 0.6% and 6.9 ± 0.5%, while NREM correspondingly increased to 37.5 ± 2.1% and 58.4 ± 1.7%. Wakefulness from P11 to P75 in dark phase increased from 37.8 ± 2.2% to 56.2 ± 2.6%, but the change in light phase was not obvious. P20 pups began to sleep more in light phase than in dark phase. The episode number of vigilance states progressively decreased with age, while the mean duration of that significantly increased. EEG power spectra in 0.5-4 Hz increased with age accompanied with prolonged duration of cortical slow wave activity. Results also indicated that the dramatic changes of sleep-wake cycle mainly occurred in the first month after birth. The novel approaches used in our study are reliable and valid for continuous PSG recording for infant rats and unravel the ontogenetic features of sleep-wake cycle.