Neuronal cell populations in circumoral nerve ring of sea cucumber Apostichopus japonicus: Ultrastructure and transcriptional profile.

The echinoderm nervous system has been studied as a model for understanding the evolution of the chordate nervous system. Neuronal cells are essential groups that release a 'cocktail' of messenger molecules providing a spectrum of biological actions in the nervous system. Among echinoderms, most evidence on neuronal cell types has been obtained from starfish and sea urchin. In sea cucumbers, most research has focused on the location of neuronal cells, whereas their transcriptional features have rarely been investigated. Here, we observed the ultrastructure of neuronal cells in the sea cucumber, Apostichopus japonicus. The transcriptional profile of neuronal cells from the circumoral nerve ring (CNR) was investigated using single-cell RNA sequencing (scRNA-seq), and a total of six neuronal cell types were identified. 26 neuropeptide precursor genes (NPPs) and 28 G-protein-coupled receptors (GPCR) were expressed in the six neuronal cell types, comprising five NPP/NP-GPCR pairs. Unsupervised pseudotime analysis of neuronal cells showed their different differentiation status. We also located the neuronal cells in the CNR by immunofluorescence (IF) and identified the potential hub genes of key cell populations. This broad resource serves as a valuable support in the development of cell-specific markers for accurate cell-type identification in sea cucumbers. It also contributes to facilitating comparison across species, providing a deeper understanding of the evolutionary processes of neuronal cells.

Morphology and Chemical Messenger Regulation of Echinoderm Muscles.

The muscular systems of echinoderms play important roles in various physiological and behavioral processes, including feeding, reproduction, movement, respiration, and excretion. Like vertebrates, echinoderm muscle systems can be subdivided into two major divisions, somatic and visceral musculature. The former usually has a myoepithelial organization, while the latter contains muscle bundles formed by the aggregation of myocytes. Neurons and their processes are also detected between these myoepithelial cells and myocytes, which are capable of releasing a variety of neurotransmitters and neuropeptides to regulate muscle activity. Although many studies have reported the pharmacological effects of these chemical messengers on various muscles of echinoderms, there has been limited research on their receptors and their signaling pathways. The muscle physiology of echinoderms is similar to that of chordates, both of which have the deuterostome mode of development. Studies of muscle regulation in echinoderms can provide new insights into the evolution of myoregulatory systems in deuterostomes.

A Putative Role of Vasopressin/Oxytocin-Type Neuropeptide in Osmoregulation and Feeding Inhibition of Apostichopus japonicus.

Vasopressin/oxytocin (VP/OT)-type neuropeptide is an ancient neurophysin-associated neuropeptide and has been intensively studied to be involved in multiple physiological processes in protostomian and deuterostome vertebrates. However, little is known about the functions of VP/OT-type neuropeptide in deuterostome invertebrates especially in echinoderms. Here, we firstly report VP/OT-type neuropeptide signaling in an important economic species, Apostichopus japonicus, which is widely cultured in Asia, with high nutritional and medicinal values. Molecular characterization analysis of holotocin and its precursor revealed the highly conserved features of VP/OT family. The candidate receptor for holotocin (AjHOR) was confirmed to be able to activate the signaling via cAMP-PKA and possible Ca2+-PKC pathway, and further activated the downstream ERK1/2 cascade. Holotocin precursor expression profile showed that they were mainly concentrated in circumoral nerve ring. Furthermore, in vitro pharmacological experiments demonstrated that holotocin caused contractile responses in preparations from A. japonicus. And in vivo functional studies indicated that short-term injection of holotocin resulted in body bloat and long-term injection resulted in reduced body mass, suggesting potential roles of holotocin in osmoregulation and feeding co-inhibition with holotocin-CCK. Our findings provided a comprehensive description of AjHOR-holotocin signaling, revealed ancient roles of holotocin in osmoregulation and feeding inhibition by controlling muscle contractions.

MicroRNA expression in osteoarthritis: a meta-analysis.

Osteoarthritis (OA) is one of the most prevalent musculoskeletal diseases globally, leading to chronic disability and poor prognosis. One of the approaches for optimizing OA treatment is to find early effective diagnostic biomarkers. The contribution of microRNAs (miRNAs) in OA progression is now being increasingly recognized. This review provides a comprehensive summary on studies reporting the expression profiling of miRNAs in OA and associated signaling pathways. We performed a systematic search of the Embase, Web of Science, PubMed, and Cochrane library databases. This systematic review is reported according to the PRISMA checklist. Studies which identified miRNAs with aberrant expression compared to controls during OA progression were included, and a meta-analysis was performed. Results from the random effects model were provided as log10 odds ratios (logORs) and 95% confidence intervals. Sensitivity analysis was conducted to confirm the accuracy of the results. Subgroup analysis was conducted based on tissue source. The target genes of miRNAs identified in this study were extracted from the MiRWalk database, and these target genes were enriched in Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways. A total of 191 studies reporting 162 miRNAs were included in our meta-analysis. Among them, 36 miRNAs distributed across 96 studies were expressed in the same direction in at least two studies (13 up-regulated and 23 down-regulated). Subgroup analysis of tissue source revealed that the highest number of studies was conducted using articular cartilage, where the most up-regulated miRNAs were miR-146a-5p (logOR 7.355; P < 0.001) and miR-34a-5p (logOR 6.955; P < 0.001), and the most down-regulated miRNAs were miR-127-5p (logOR 6.586; P < 0.001) and miR-140-5p (logOR 6.373; P < 0.001). Enrichment analysis of 752 downstream target genes of all identified miRNAs was performed, and the regulatory relationships among them were displayed. Mesenchymal stem cells and transforming growth factor-ß were found to be the most important downstream effectors regulated by miRNA in OA. This study highlighted the importance of miRNA signaling in OA progression and identified a number of prominent miRNAs including miR-146a-5p, miR-34a-5p, miR-127-5p, and miR-140-5p which might be considered as potential biomarkers for OA.

Comparative Analysis of the Self-Propelled Locomotion of a Pitching Airfoil near the Flat and Wavy Ground.

In this paper, a pitching airfoil near flat and wavy ground is studied by numerical simulations. The kinematic features of the airfoil and the flow field around it are analyzed to reveal unsteady vorticity dynamics of the self-propelled airfoil in ground effect. The optimal pitching periods at different initial heights above flat ground are obtained, which make the pitching airfoil achieve the maximum lift-to-drag ratio. Compared with flat ground, at the same initial height, the optimal pitching periods vary with the shape of ground. The structure and the strength of the wake vortices shedding from the airfoil are adjusted by the wavelength of ground. This leads to the changes of amplitude and occurrence times of the peak and valley of lift and drag force. The results obtained in this study can provide some inspiration for the design of underwater vehicles in the ground effect.

Nervous System Development and Neuropeptides Characterization in Embryo and Larva: Insights from a Non-Chordate Deuterostome, the Sea Cucumber Apostichopus japonicus.

Here, we described the complex nervous system at five early developmental stages (blastula, gastrula, auricularia, doliolaria and pentactula) of a holothurian species with highly economic value, Apostichopus japonicus. The results revealed that the nervous system of embryos and larvae is mainly distributed in the anterior apical region, ciliary bands or rings, and the feeding and attachment organs, and that serotonergic immunoreactivity was not observed until the embryo developed into the late gastrula; these are evolutionarily conserved features of echinoderm, hemichordate and protostome larvae. Furthermore, based on available transcriptome data, we reported the neuropeptide precursors profile at different embryonic and larval developmental stages. This analysis showed that 40 neuropeptide precursors present in adult sea cucumbers were also identified at different developmental stages of embryos and larvae, and only four neuropeptide precursors (SWYG precursor 2, GYWKDLDNYVKAHKT precursor, Neuropeptide precursor 14-like precursor, GLRFAmprecursor-like precursor) predicted in adults were absent in embryos and larvae. Combining the quantitative expression of ten specific neuropeptide precursor genes (NPs) by qRT-PCR, we revealed the potential important roles of neuropeptides in embryo development, feeding and attachment in A. japonicus larvae. In conclusion, this work provides novel perspectives on the diverse physiological functions of neuropeptides and contributes to understanding the evolution of neuropeptidergic systems in echinoderm embryos and larvae.

Molecular and functional characterization of the luqin-type neuropeptide signaling system in the sea cucumber Apostichopus japonicus.

The functional characteristics of neuropeptides in marine invertebrates have attracted significant attention recently although functional studies of luqin-type neuropeptides are still very limited, especially in deuterostomes. The sea cucumber, Apostichopus japonicus, is a representative species of deuterostomian Holothurian invertebrates. The species has high nutritional and medicinal value in China. In this study, we report the first comprehensive histological, biochemical and pharmacological characterization of luqin-type neuropeptide signaling in the sea cucumber A. japonicus. The A. japonicus luqin-like neuropeptide precursor (AjLQP) contains a single typical deuterostomian luqin-like neuropeptide AjLQ with an xFxRWamide motif. AjLQ was identified as the ligand for a luqin-type neuropeptide receptor AjLQR, that was previously predicted to be a tachykinin-type receptor, and triggers a rapid intracellular mobilization of Ca2+, followed by receptor internalization and a transient increase in ERK1/2 phosphorylation. In situ hybridization, immunohistochemistry and qRT-PCR analysis revealed extensive expression of AjLQP and AjLQ in A. japonicus tissues, especially in locomotion-related organs. In vitro pharmacological tests revealed that AjLQ caused 12.69% ± 1.99% (p < 0.01) relaxation of longitudinal muscle preparations at 10-7 M concentration. Furthermore, we observed significantly increased expression of AjLQP (about 17.63 fold, p < 0.01) in intestine of deeply aestivating sea cucumbers, which suggests that AjLQ might be involved in feeding inhibition during aestivation. The present study provides a first insight into the experimental characterization of luqin-type neuropeptide signaling in a sea cucumber. The results will broaden our understanding of the potential function of neuropeptides during important biological processes in marine invertebrates and provide theoretical support for optimizing sea cucumber aquaculture technology.

Preparation and properties of SiC/SiOX heterojunction fiber reinforced porous SiC composite materials.

Porous silicon carbide composite ceramics were prepared by partial sintering method and sacrificial silicon, with phenolic resin applied as carbon template, and silicon powder as silicon source and pore-forming agent. It showed a composite structure of SiC/SiO2/SiC sandwich shell structure and SiC/SiOX heterojunction nanofiber. Through an investigation into the effect of carbon-silicon atomic ratio on the structure and thermodynamic properties of porous SiC. It was revealed that the carbon network formed by the phenolic resin played a role in restricting the position of the silicon powder and building a regularly-arranged porous SiC structure. The prepared samples reached a porosity of 50-75% while exhibiting a low thermal conductivity ranging from 0.74 to 1.3 W/(m·K), which is attributed to the nanoscale phonon dispersion mechanism and nanofiber thermal insulation, together with high stiffness. Porous ceramics demonstrate both mechanical and thermal insulation properties, which makes them applicable as thermal protection materials for hypersonic aircraft. This is effectively in reducing the aerodynamic thermal effects of hypersonic aircraft.

Synergistic Effect of Sic Particles and Whiskers on the Microstructures and Mechanical Properties of Ti(C,N)-Based Cermets.

The microstructure and mechanical properties of Ti(C,N)-based cermets with the addition of the SiC particles (SiCp) and SiC whiskers (SiCw), were systematically studied in this work. Firstly, the effect of SiCp on the cermets was investigated independently to determine the considerable total amounts of additives, and the results showed that 2.0 wt.% SiCp would lead to optimal properties of the cermet. Then, the influence of SiCp and SiCw additions with the variable ratio on the cermets was studied. The results indicated that when 1.5 wt.% SiCp and 0.5 wt.% SiCw were added; the cermets appeared with the best comprehensive properties, and the transverse rupture strength, hardness, and the fracture toughness of the cermets reached 2520.8 MPa, 88.0 HRA, and 16.56 MPa·m1/2, respectively. This was due to the synergistic strengthening and toughening effect afforded by the reasonable SiCp and SiCw addition, from which the smallest grain size, as well as the most uniform, and completed core-rim structure of the cermets, were achieved.

Application of Coagulation-Membrane Rotation to Improve Ultrafiltration Performance in Drinking Water Treatment.

The combination of conventional and advanced water treatment is now widely used in drinking water treatment. However, membrane fouling is still the main obstacle to extend its application. In this study, the impact of the combination of coagulation and ultrafiltration (UF) membrane rotation on both fouling control and organic removal of macro (sodium alginate, SA) and micro organic matters (tannic acid, TA) was studied comprehensively to evaluate its applicability in drinking water treatment. The results indicated that membrane rotation could generate shear stress and vortex, thus effectively reducing membrane fouling of both SA and TA solutions, especially for macro SA organics. With additional coagulation, the membrane fouling could be further reduced through the aggregation of mediate and macro organic substances into flocs and elimination by membrane retention. For example, with the membrane rotation speed of 60 r/min, the permeate flux increased by 90% and the organic removal by 35% in SA solution, with 40 mg/L coagulant dosage, with an additional 70% increase of flux and 5% increment of organic removal to 80% obtained. However, too much shear stress could intensify the potential of fiber breakage at the potting, destroying the flocs and resulting in the reduction of permeate flux and deterioration of effluent quality. Finally, the combination of coagulation and membrane rotation would lead to the shaking of the cake layer, which is beneficial for fouling mitigation and prolongation of membrane filtration lifetime. This study provides useful information on applying the combined process of conventional coagulation and the hydrodynamic shear force for drinking water treatment, which can be further explored in the future.

Investigation on the micromorphology and thermophysical properties of NaNO3 heat storage materials modified by solution combustion.

Nitrate has a wide temperature range, wide operating temperature, low vapor pressure, low cost, strong heat transfer and stable chemical properties. It is widely used in solar thermal power generation heat storage material. In this paper, the alkali salt NaNO3 was modified by solution combustion method with citric acid as fuel. The structure and thermal properties of the prepared salts were studied by field emission scanning electron microscopy (FE-SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR) and differential scanning calorimetry (DSC). The results show that the solution combustion process improves the structure and thermal properties of NaNO3, and the resulting product has a new phase. The particle size and microscopic morphology of the prepared salt were changed. As the proportion of fuel increases, the hollow cuboid structure gradually grows on the surface and inside of the modified salt. The microstructure obtained is different at different ignition temperatures, and a finer and even rod-like structure is obtained at an ignition temperature of 600 °C. The specific heat capacity of all modified samples has been improved, among which solid specific heat and liquid specific heat have increased the most, respectively 3.10 J/g·K and 3.19 J/g·K, which are 140.31% and 131.16% higher than the base salt, respectively. This work not only studies the specific heat capacity of NaNO3 modified by solution combustion, but also explores the effect of micromorphology and new phase formation on its performance, which provides innovative ideas for improving the specific heat capacity of molten salt heat storage materials.

New synthetic flavone derivatives induce apoptosis of hepatocarcinoma cells.

Natural flavonoids have broad biological activity, including anticancer. In this study, a series of novel flavone derivatives were synthesized with the substitutions of chlorine, isopropyl, methoxy, and nitro groups on the benzene ring of flavone skeleton to develop effective anticancer agents. Antiproliferative assays showed that the synthesized chemicals possess notable activity against hepatocarcinoma cells (HepG-2); in particular, the compound 6f with chlorine and dimethoxy modifications at the two benzene rings showed an IC(50) at 1.1 microM to HepG-2. The 6f also displayed marked anticancer activity towards a panel of cancer cells, including nasopharyngeal carcinoma cells (CNE-2 and CNE-1), breast adenocarcinoma cell (MCF-7), and epithelial carcinoma cells (Hela). Exposing HepG-2 cells to compound 6f at 10 microM induced chromatin condensation, nuclear disassembly, and DNA fragmentation. In 6f-treated HepG-2 cells, the sub-G(0) population was remarkably increased; and in these cells, both caspase-8 and caspase-9 activity was significantly increased, which in turn activated caspase-3. In addition, proapoptotic Bax was upregulated by compound 6f while the antiapoptotic Bcl-2 was downregulated. Taken together, our data suggest that the new flavonoid derivative 6f triggers apoptosis through both death-receptor and mitochondria-dependent intrinsic pathways, being a potent therapeutic agent against hepatocarcinoma.

The design, synthesis, and anti-tumor mechanism study of N-phosphoryl amino acid modified resveratrol analogues.

A novel series of trans-N-phosphoryl amino acid modified resveratrol analogues were synthesized and evaluated in vitro for their cytotoxic effects against CNE-1 and CNE-2 cell lines. These analogues showed good anti-proliferative activity, among which 8d, 8e, 8j, and 9d displayed much stronger inhibition effect than resveratrol and 8d showed the most potent activity with IC(50) value at 3.45+/-0.82microM. The anti-tumor effects of 8d, 8e, 8j, and 9d were due to the induction of apoptosis, confirmed by the DNA fragmentation and flow cytometry analysis using PI (propidium iodide) staining and Annexin-V-FITC/PI staining assay. The PI staining assay also showed that 8d, 8e, 8j, and 9d caused cell cycles arrest at G(0)-G(1) phase which finally led to cell apoptosis. Further mechanism study on compound 8d against CNE-2 cells has shown the PARP cleavage, which is a hallmark of caspase-3 activation, as well as the activation of caspase-9, and the intracellular ROS generation. These results all suggest that 8d induced a mitochondrial-dependent apoptosis pathway.

Synthesis and potent antileukemic activities of 10-benzyl-9(10H)-acridinones.

A novel series of 10-benzyl-9(10H)-acridinones and 1-benzyl-4-piperidones were synthesized and tested for their in vitro antitumor activities against CCRF-CEM cells. Assay-based antiproliferative activity study using CCRF-CEM cell lines revealed that the acridone group and the substitution pattern on the benzene unit had significant effect on cytotoxicity of this series of compounds, among which 10-(3,5-dimethoxy)benzyl-9(10H)-acridinone (3b) was found to be the most active compound with IC(50) at about 0.7 microM. Compound 3b was also found to have antiproliferative activity against two other human leukemic cell lines K562 and HL60 using the MTT assay. The antitumor effect of 3b is believed to be due to the induction of apoptosis, which is further confirmed by PI (Propidium iodide) staining and Annexin V-FITC/PI staining assay using flow cytometry analysis.