Identification of toll-like receptor family and the immune function of new Sptlr-6 gene of Scylla paramamosain.

As a crucial member of pattern-recognition receptors (PRRs), the Tolls/Toll-like receptors (TLRs) gene family has been proven to be involved in innate immunity in crustaceans. In this study, nine members of TLR gene family were identified from the mud crab (Scylla paramamosain) transcriptome, and the structure and phylogeny of different SpTLRs were analyzed. It was found that different SpTLRs possessed three conserved structures in the TIR domain. Meanwhile, the expression patterns of different Sptlr genes in examined tissues detected by qRT-PCR had wide differences. Compared with other Sptlr genes, Sptlr-6 gene was significantly highly expressed in the hepatopancreas and less expressed in other tissues. Therefore, the function of Sptlr-6 was further investigated. The expression of the Sptlr-6 gene was up-regulated by Poly I: C, PGN stimulation and Vibrio parahaemolyticus infection. In addition, the silencing of Sptlr-6 in hepatopancreas mediated by RNAi technology resulted in the significant decrease of several conserved genes involved in innate immunity in mud crab after V. parahaemolyticus infection, including relish, myd88, dorsal, anti-lipopolysaccharide factor (ALF), anti-lipopolysaccharide factor 2 (ALF-2) and glycine-rich antimicrobial peptide (glyamp). This study provided new knowledge for the role of the Sptlr-6 gene in defense against V. parahaemolyticus infection in S. paramamosain.

Theoretical Study on the Photoemission Performance of a Transmission Mode In0.15Ga0.85As Photocathode in the Near-Infrared Region.

Benefiting from a high quantum efficiency, low thermal emittance, and large absorption coefficient, InxGa1-xAs is an excellent group III-V compound for negative electron affinity (NEA) photocathodes. As the emission layer, InxGa1-xAs, where x = 0.15, has the optimal performance for detection in the near-infrared (NIR) region. Herein, an NEA In0.15Ga0.85As photocathode with Al0.63Ga0.37As as the buffer layer is designed in the form of a transmission mode module. The electronic band structures and optical properties of In0.15Ga0.85As and Al0.63Ga0.37As are calculated based on density functional theory. The time response characteristics of the In0.15Ga0.85As photocathode have been fully investigated by changing the photoelectron diffusion coefficient, the interface recombination velocity, and the thickness of the emission layer. Our results demonstrate that the response time of the In0.15Ga0.85As photocathode can be reduced to 6.1 ps with an incident wavelength of 1064 nm. The quantum efficiency of the In0.15Ga0.85As photocathode is simulated by taking into account multilayer optical thin film theory. The results indicate that a high quantum efficiency can be obtained by parameter optimization of the emission layer. This paper provides significant theoretical support for the applications of semiconductor photocathodes in the near-infrared region, especially for the study of ultrafast responses in the photoemission process.

Landscapes of gut microbiome and bile acid signatures and their interaction in HBV-associated acute-on-chronic liver failure.

Introduction: Submassive hepatic necrosis (SMHN, defined as necrosis of 15-90% of the entire liver on explant) is a likely characteristic pathological feature of ACLF in patients with hepatitis B cirrhosis. We aimed to comprehensively explore microbiome and bile acids patterns across enterhepatic circulation and build well-performing machine learning models to predict SMHN status. Methods: Based on the presence or absence of SMHN, 17 patients with HBV-related end-stage liver disease who received liver transplantation were eligible for inclusion. Serum, portal venous blood, and stool samples were collected for comparing differences of BA spectra and gut microbiome and their interactions. We adopted the random forest algorithm with recursive feature elimination (RF-RFE) to predict SMHN status. Results: By comparing total BA spectrum between SMHN (-) and SMHN (+) patients, significant changes were detected only in fecal (P = 0.015). Compared with the SMHN (+) group, the SMHN (-) group showed that UDCA, 7-KLCA, 3-DHCA, 7-KDCA, ISOLCA and α-MCA in feces, r-MCA, 7-KLCA and 7-KDCA in serum, γ-MCA and 7-KLCA in portal vein were enriched, and TUDCA in feces was depleted. PCoA analysis showed significantly distinct overall microbial composition in two groups (P = 0.026). Co-abundance analysis showed that bacterial species formed strong and broad relationships with BAs. Among them, Parabacteroides distasonis had the highest node degree. We further identified a combinatorial marker panel with a high AUC of 0.92. Discussion: Our study demonstrated the changes and interactions of intestinal microbiome and BAs during enterohepatic circulation in ACLF patients with SMHN. In addition, we identified a combinatorial marker panel as non-invasive biomarkers to distinguish the SMHN status with high AUC.

A member of the immunoglobulin superfamily lrig-1 might be involved in the immune priming of Scylla paramamosain in response to the infection and re-infection by Vibrio parahaemolyticus.

A member of the immunoglobulin superfamily designated leucine-rich repeats and immunoglobulin-like domains protein-1 (lrig-1) encoding a protein with 1109 amino acids with a characteristic IGc2 domain was identified from the transcriptome data of mud crab Scylla paramamosain. Lrig-1 contained: one signaling peptide; one LRR_NT domain; nine LRR domains; three LRR_TYP domains; one LRR_CT domain; three IGc2 regions; one transmembrane region; C-terminal cytoplasmic tail. lrig-1 was widely expressed in all tissues of mud crab and was responsive in hemocytes to first and second Vibrio parahaemolyticus infections. lrig-1 knockdown mediated by RNAi repressed expression of several antimicrobial peptides significantly. Its orthologs in 19 crustacean species were identified and showed high conservation. These results suggest that lrig-1 have a vital role in mud crabs against V. parahaemolyticus infection through expression of multiple antimicrobial peptides. The results obtained in the present study imply the potential roles the lrig-1 played in immune priming in crabs.

Recent Advances in Strategies to Combat Bacterial Drug Resistance: Antimicrobial Materials and Drug Delivery Systems.

Bacterial infection is a common clinical disease. Antibiotics have saved countless lives since their discovery and are a powerful weapon in the fight against bacteria. However, with the widespread use of antibiotics, the problem of drug resistance now poses a great threat to human health. In recent years, studies have investigated approaches to combat bacterial resistance. Several antimicrobial materials and drug delivery systems have emerged as promising strategies. Nano-drug delivery systems for antibiotics can reduce the resistance to antibiotics and extend the lifespan of novel antibiotics, and they allow targeting drug delivery compared to conventional antibiotics. This review highlights the mechanistic insights of using different strategies to combat drug-resistant bacteria and summarizes the recent advancements in antimicrobial materials and drug delivery systems for different carriers. Furthermore, the fundamental properties of combating antimicrobial resistance are discussed, and the current challenges and future perspectives in this field are proposed.

Lymphocyte Membrane- and 12p1-Dual-Functionalized Nanoparticles for Free HIV-1 Trapping and Precise siRNA Delivery into HIV-1-Infected Cells.

Despite the success of small interfering RNA (siRNA) in clinical settings and its potential value in human immunodeficiency virus (HIV) therapy, the rapid clearance and absence of precise delivery to target cells still hinder the therapeutic effect of siRNA. Herein, a new system, which can escape immune recognition, has HIV-1 neutralizing capacity, and the ability to deliver siRNA specifically into HIV-1-infected cells, is constructed by functionalizing siRNA delivery lipid nanoparticles with the lymphocyte membrane and 12p1. The constructed system is shown to escape uptake by the mononuclear phagocyte system. The constructed system exhibits strong binding ability with gp120, thus displaying distinguished neutralizing breadth and potency. The constructed system neutralizes all tested HIV-1 pseudotyped viruses with a geometric mean 80% inhibitory concentration (IC80) of 29.75 µg mL-1 and inhibits X4-tropic HIV-1 with an IC80 of 64.20 µg mL-1 , and R5-tropic HIV-1 with an IC80 of 16.39 µg mL-1 . The new system also specifically delivers siRNA into the cytoplasm of HIV-1-infected cells and exhibits evident gene silencing of tat and rev. Therefore, this new system can neutralize HIV-1 and deliver siRNA selectively into HIV-1-infected cells and may be a promising therapeutic candidate for the precise therapy of HIV.

dmrtb1 is involved in the testicular development in Larimichthys crocea.

In brief: dmrtb1 performs critical functions in sex determination/differentiation and gonadal development in many organisms, but its role in teleost is rarely studied. Through gene cloning, in situ hybridization, and RNA interference technology, the function of dmrtb1 in testicular development of large yellow croaker (Larimichthys crocea) was studied; our study will be helpful in understanding further the molecular regulation mechanism of Lcdmrtb1/Lcdmrt6 in testicular development in L. crocea, and our results enrich the theory of fish dmrts involved in reproductive regulation and provide a new idea for sex control breeding of L. crocea by manipulating reproductive pathway. Abstract: Doublesex- and mab-3-related transcription factor B1 (dmrtb1/dmrt6) belongs to one of the members of DMRT family, which performs critical functions in sex determination and differentiation, gonadal development, and functional maintenance. However, knowledge of its exact mechanism remains unclear in teleost. Very little is known about the role of dmrtb1 in the gonad development of Larimichthys crocea. In this study, a dmrtb1 homolog in L. crocea named as Lcdmrtb1 with the full-length cDNA was isolated and characterized. Except for the conserved DM domain, the other regions had low homology. Of the tissues sampled, Lcdmrtb1 was only found to be highly expressed in the testis. In situ hybridization of testis revealed Lcdmrtb1 in both spermatogonia and spermatocytes. After Lcdmrtb1 interference in the testis cells (LYCT) of L. crocea, the expression levels of Lcdmrtb1 and Lcdmrt1 were significantly decreased; subsequently, testicular cell morphology changed from fibrous to round and their growth rate slowed. Similarly, the expression levels of Lcdmrtb1, Lcdmrt1, sox9a/b, and amh were significantly decreased after RNAi in the testis. Furthermore, it was discovered that the spermatogonia had disappeared, and the Sertoli cells had been reduced. The results of immunohistochemistry showed that the expression of Sox9 protein in the testis was not detected after dmrtb1 was knocked down. These results indicated that the absence of Lcdmrtb1 not only greatly inhibited cell growth and destroyed the morphology of testis cells but also down-regulated Lcdmrt1 expression in the testis. This study will be helpful in understanding further the molecular regulation mechanism of Lcdmrtb1/Lcdmrt6 in testicular development in L. crocea.

A Membrane Curvature Modulated Lipopeptide to Broadly Combat Multidrug-Resistant Bacterial Pneumonia with Low Resistance Risk.

The extensive spread of multidrug resistance to Gram-negative bacteria has become a huge threat to human health, where peptide-based antibacterial agents have emerged as a powerful star weapon. Here we report a lipopeptide (LP-20) constructed nanomicelle with a different antibacterial mechanism of membrane curvature modulation, which induced dynamic membrane fission resulting in acceleration and enhancement of antibacterial activity to clinically isolated ESKAPE strains, including multidrug-resistant (MDR) pathogens. The minimum inhibitory concentration was reduced to 2-10 µM, and the minimum duration for killing was shortened to less than an hour by LP-20. This is an improvement over antimicrobial peptides and traditional antibiotics, such as ciprofloxacin and tetracycline, significantly enhancing antibacterial activity for MDR, and we observed no acquisition of resistance for one month. This accelerated germicidal mechanism was attributed to multitargeting with lipopolysaccharides, phosphoethanolamine, phosphatidylglycerol, and cardiolipin, and the synergetic interactions induced a high curvature of the bacterial membrane, which facilitated simultaneously efficient damage to both inner and outer membrane. The LP-20 effectively prolonged the lifetime of myositis mice with Escherichia coli MDR and pneumonia mice with Klebsiella pneumoniae through a hepatic metabolism with ignorable toxicity. This study provides critical information for the fabrication of lipopeptide-based nano-antibiotics for the efficient control of intractable MDR caused by Gram-negative pathogens.

Immune function modulation during artificial ovarian maturation in Japanese eel (Anguilla japonica): A transcriptome profiling approach.

The Japanese eel (Anguilla japonica) experiences dramatic internal and external environmental changes during its transoceanic reproductive migrations. Here, we assess immune function changes in the primary and secondary immune organs (head kidney and spleen) of A. japonica during artificial ovarian maturation at the previtellogenic (PV), midvitellogenic (MV), and ovulating (OV) stages by transcriptome analyses. Stress responses were also assessed by determining the serum concentrations of lysozyme, alkaline phosphatase, acid phosphatase, total antioxidant capacity, and superoxide dismutase. Our results showed that together with increased serum 17ß-estrogen and testosterone, lysozyme activity and antioxidant capacity were suppressed during artificial ovarian maturation. Comparisons across these developmental stages identified 60 (head kidney) and 36 (spleen) differentially expressed genes associated with the immune system. Genes related to the key activation markers of innate immune function, such as CXCL10, CXCL11, CCL20, HSP90B, MMP9, and MMP13, were upregulated and significantly enriched in the interleukin-17 signaling pathway. Adaptive immune function-related genes (IGM and MHC1) were upregulated in the head kidney from PV to MV, and their levels increased thereafter in the spleen. Moreover, a correlation between Pax5 expression and IGM expression in the spleen of MV (IGM+/Pax5+) and OV (IGM++/Pax5-) stage suggests that adaptive immune function was enhanced during ovarian maturation. To our knowledge, the present study is the first to describe transcriptome profiling of immune organs during ovarian maturation in teleost. Our findings suggest that the interleukin-17 pathway and IgM may play important roles in spawning.

Integration of RNAi and RNA-seq uncovers the regulation mechanism of DDX20 on vitellogenin expression in Scylla paramamosain.

Vitellogenesis in crustaceans is controlled by several steroid hormones. In humans, the expression of SF-1, a gene that regulates gonadal development and the synthesis of steroid hormones, is affected by DDX20. However, how the homologous gene FTZ-F1 is regulated by DDX20 and its association with vitellogenesis remains unknown in the mud crab Scylla paramamosain. In this study, SpDDX20 and SpFTZ-F1 were identified in the transcriptome of mature ovarian tissue from the mud crab. qRT-PCR results revealed that the expression levels of SpFTZ-F1 and SpVTG in the ovaries of crab in the experimental group injected with dsDDX20 (EO) were significantly higher (P < 0.05) than those in the negative control group injected with dsEGFP (NO) and the blank control group injected with SPSS (BO). The differentially expressed genes (DEGs) identified by comparative transcriptome analysis of the EO group and NO group were enriched into five pathways related to ovarian steroidogenesis. The expression of CYP17, CYP3A4, CYP1A1 and 3ß-HSD were up-regulated in pathways related to steroid hormone production and biosynthesis. The expression of the INSR, IRS and PI3K genes in the insulin signaling pathway were significantly increased (P < 0.05). The expression level of the TGF-ß gene was up-regulated (P < 0.05) in the transforming growth factor pathway, whereas the expression level of the Smad2 gene was down-regulated (P < 0.05). The expression of GnRHR, GS, AC and PKA genes in the gonadotropin-releasing hormone signaling pathway were up-regulated. Our data provide a foundation for investigating the relationship between DDX20 and FTZ-F1 in the regulation of vitellogenin expression in S. paramamosain.

Effects of Two Kinds of Extracts of Cistanche deserticola on Intestinal Microbiota and Its Metabolism.

Cistanche deserticola belongs to the Liedang family. Known as "desert ginseng", it has high medicinal value and plays important roles in endocrine regulation, neuroprotection, immune regulation, and other processes. Some studies have shown that single substances such as polysaccharides and phenylethanolside can affect intestinal microbiota, but few studies have studied the synergistic effect of various components in Cistanche deserticola extracts on intestinal microbiota. Therefore, in this study, through an in vitro digestion model (Changdao Moni, CDMN) combined with 16S rRNA gene amplification sequencing technology and untargeted metabolomics technology, it was found that the two extracts all had significant effects on the enteric cavity and mucosal flora. Both extracts inhibited Bacteroides in the intestinal cavity and Parabacteroides and Ruminococcus 2 in the intestinal mucosa and promoted Bifidobacterium and Prevotella in the intestinal cavity and Megasphaera in the intestinal mucosa. The aqueous extract also inhibited Phascolarctobacterium. Both extracts also significantly increased the production of short-chain fatty acids, especially butyrate. The intake of extract had significant effects on the metabolic pathways related to amino acids and lipids. Indoles were upregulated by the aqueous extract but downregulated by the alcohol extract. In addition, the extract also had a significant effect on the hemolytic phosphorus esters. In conclusion, the two kinds of extracts have different effects on intestinal microbiota and its metabolism. This study provides guiding significance for the edibility and food development of Cistanche deserticola.

Defect- and Interface-Induced Dielectric Loss in ZnFe2O4/ZnO/C Electromagnetic Wave Absorber.

Controlling defects and interfaces in composite absorbers can effectively regulate electromagnetic (EM) parameters and enhance the electromagnetic wave (EMW) absorption ability, but the mechanism still needs to be further elucidated. In this study, ZnFe2O4/ZnO/C composite was synthesized via the hydrothermal method followed by post-annealing in different atmospheres. Defects and interfaces were characterized by Raman, PL spectroscopy, XPS and TEM, and their relationship with dielectric loss and EMW absorption performance was discussed in detail. Results show that the N2-annealed ZnFe2O4/ZnO/C composite with abundant defects and interfaces as well as an optimized composition exhibits excellent EMW dissipation ability, with a RLmin value of -17.4 dB and an fe of 3.85 GHz at a thickness of 2.28 mm. The excellent EMW absorption performance originates from suitable impedance matching, significant conduction loss and strong dielectric loss (interfacial polarization, diploe polarization and defect polarization) dominated by lattice defects and interfaces. This study provides a view into the relationship between defects, interfaces, EM parameters and EMW absorption ability, and also suggests an effective way to promote EMW dissipation ability of the absorbers by controlling defects and interfaces.

Advances in Cellulose-Based Hydrogels for Biomedical Engineering: A Review Summary.

In recent years, hydrogel-based research in biomedical engineering has attracted more attention. Cellulose-based hydrogels have become a research hotspot in the field of functional materials because of their outstanding characteristics such as excellent flexibility, stimulus-response, biocompatibility, and degradability. In addition, cellulose-based hydrogel materials exhibit excellent mechanical properties and designable functions through different preparation methods and structure designs, demonstrating huge development potential. In this review, we have systematically summarized sources and types of cellulose and the formation mechanism of the hydrogel. We have reviewed and discussed the recent progress in the development of cellulose-based hydrogels and introduced their applications such as ionic conduction, thermal insulation, and drug delivery. Also, we analyzed and highlighted the trends and opportunities for the further development of cellulose-based hydrogels as emerging materials in the future.

Cloning, expression, and function of the Spdmrt-like gene in Scylla paramamosain.

BACKGROUND: The mud crab Scylla paramamosain is an economically important species for aquaculture in China and has sexually dimorphic between females and males. Understanding sex differentiation in this species is essential for the development of monosex aquaculture. The Dmrt genes play a vital role in sex differentiation in animals. METHODS AND RESULTS: In this study, two dmrt-like transcript variants, Spdmrt-like-tv1 and Spdmrt-like-v2, were cloned. SpDmrt-like-tv1 contained a DM domain, while SpDmrt-like-tv2 contained a DM and a DMA domain. Spdmrt-like-tv1 and Spdmrt-like-tv2 were both specifically expressed in testis. During testicular development, the expression level of Spdmrt-like-tv1 increased from stage I to stage II (P > 0.05) and then decreased from stage II to stage III (P < 0.05). The expression level of Spdmrt-like-tv2 in stages I and II was significantly higher than that in stage III (P < 0.05). During embryonic development, the expression level of Spdmrt-like-tv1 was higher in the mid-embryonic stage compared with the early and late stages, but the differences were not significant. Moreover, the expression level of Spdmrt-like-tv2 was stable and remained high throughout embryonic development. Furthermore, the expression level of Spdmrt-like-tv2 was significantly higher than that of Spdmrt-like-tv1. Knockdown of Spdmrt-like variants indicated that the regulative target gene of Spdmrt-like-tv1 was Spsox21, and the regulative target genes of Spdmrt-like-tv2 were Spfoxl2 and Spsox21. Combined with the results in our previously published peer-reviewed articles that the expression of Spfoxl2 in the testis was significantly higher than that in the ovary, and Spfoxl2 negatively regulated Spvtg expression. Spsox21 played a role in the development and maintenance of testis as well as in the process of neural development and regulation of body segmentation. CONCLUSION: Therefore, we suggest that Spdmrt-like-tv1 and Spdmrt-like-tv2 might be involved in testicular development and embryonic development, and Spdmrt-like-tv2 might play more important roles in these two developmental processes by regulating the expression of Spfoxl2 and Spsox21 due to its high expression.

Hydrochemical characteristics and quality assessment of shallow groundwater in Yangtze River Delta of eastern China.

Water resource is in high demand within the Yangtze River Delta, given its developed economy. Long-term exploitation of this resource has posed risks of artificial pollution and seawater intrusion to the shallow groundwater. This study aims to reveal the hydrochemical characteristics and health risks of shallow groundwater in the coastal plain of the Yangtze River Delta, as well as to discuss the possible factors affecting groundwater quality. Standard methods for hydrochemical parameter measurements, water quality assessment, and health risk models were applied to fulfill the objectives of the study. The results showed that the shallow groundwater was slightly alkaline, and the average values of total dissolved solids (TDS) and total hardness (TH) were 930.74 mg/L and 436.20 mg/L, respectively. The main hydrochemical types of groundwater were HCO3-Ca·Mg and HCO3-Ca·Na, accounting for 44.3% and 47.5%, respectively. In addition, As concentration was generally high, with a mean value of 0.0115 mg/L. The principal factors affecting the groundwater components include water-rock interactions (especially silicate), cation exchange, seawater intrusion, and human activities. The data also showed that As is strongly influenced by the redox of Fe, Mn, and NO3-. The results of the groundwater quality evaluation indicated that the shallow groundwater in some regions was unsuitable for drinking and agricultural irrigation. Health risk assessment showed that 44.3% of the water samples had significant health risks, which was attributed to the high As concentration. Therefore, it is urgent to establish long-term As monitoring to maintain sustainable groundwater management and drinking water safety. The results of this study provide essential data for water resource management and human health security in the Yangtze River Delta.

Comparative Transcriptome Reveals the Potential Modulation Mechanisms of Spfoxl-2 Affecting Ovarian Development of Scylla paramamosain.

Previously, we reported the identification, tissue distribution and confirmed the roles of Spfoxl-2 in regulating vitellogenin (vtg) expression in Scylla paramamosain. Here, we primally analyzed its potential target genes in the ovary with RNAi and RNA-Seq technology. By comparing the transcriptome data of two groups (ovaries that injected with EGFP and Foxl-2 siRNA, respectively), we found 645 DEGs (differentially expressed genes), including several conserved crucial genes involved in ovarian development, such as vtg, vitellogenin receptor (vtgR), adenylate cyclase (AC), cyclinB, and cell division cycle 2 (cdc2). In addition, these DEGs were also enriched in pathways related to ovary development, including relaxin signaling pathway, ovarian steroidogenesis, and progesterone-mediated oocyte maturation. Moreover, several genes were selected for qRT-PCR to validate the accuracy of the bioinformatic result. To the best of our knowledge, the current study was the first report about foxl-2 function through comparative transcriptome analysis in crustacean species, which identified not only relevant genes and pathways involved in ovarian development of S. paramamosain, but also provided new insights into the regulatory mechanisms of foxl-2 at the molecular level in crustacean.

Glycopeptide-nanotransforrs eyedrops with enhanced permeability and retention for preventing fundus neovascularization.

Efficient and non-invasive drug delivery to the fundus has always been a medical difficulty. Here, a co-assembled glycopeptide nanotransforrs (GPNTs) named MRP@DOX as a drug delivery system is reported. The MRP@DOX co-assemble nanoparticles consisting of glycopeptide, cationic peptide, and doxorubicin (DOX). The nanoparticles are positively charged with the nano-size, which can be induced transformation by legumain cleavage. Once administrate to the eyes, MRP@DOX has a high penetration through the ocular surface to specifically targets M2 macrophages in the fundus. Then, the mannose receptor mediates phagocytosis and intracellular highly expressed legumain induces its nanofibrous transformation, which contributes to a 44.7% DOX retention in cells at 24 h than that of the non-transformed controls (MAP@DOX: 5.1%). The nanofiber transformation provides an inhibition of exocytosis, which explains the higher retention of the delivered drug. In the mouse OIR model, MRP@DOX completely restores the physiological angiogenesis and reduces pathological neovascularization. Pathological neovascularization branches and cell nuclei that break through the inner limiting membrane are reduced by 55% and 72%, respectively, which are 25% and 20% less than those in the non-transformed controls. In addition, MRP@DOX also has good histocompatibility, which provides a possible strategy for non-invasive treatment of fundus diseases in the future.

RIP3 Associates with RIP1, TRIF, MAVS, and Also IRF3/7 in Host Innate Immune Signaling in Large Yellow Croaker Larimichthys crocea.

Receptor-interacting protein 3 (RIP3) has been demonstrated to be a key regulator not only in cell death pathways including apoptosis and necroptosis but also in inflammation and host immune responses. In this study, a RIP3 ortholog named Lc-RIP3 is identified in large yellow croaker (Larimichthys crocea). The open reading frame (ORF) of Lc-RIP3 is 1524 bp long and encodes a protein of 507 amino acids (aa). The deduced Lc-RIP3 protein has an N-terminal kinase domain and a C-terminal RHIM domain, and the genome organization of Lc-RIP3 is conserved in teleosts with 12 exons and 11 introns but is different from that in mammals, which comprises 10 exons and 9 introns. Confocal microscopy revealed that Lc-RIP3 is a cytosolic protein. The expression analysis at the mRNA level indicated that Lc-RIP3 is ubiquitously distributed in various tissues/organs, and could be up-regulated under poly I:C, LPS, PGN, and Pseudomonas plecoglossicida stimulation in vivo. Notably, Lc-RIP3 could induce NF-κB but not IRF3 activation. In addition, Lc-RIP3 co-expression with Lc-TRIF, Lc-MAVS, or Lc-IRF3 significantly abolishes the activation of NF-κB but enhances the induction of IRF3 activity. Moreover, NF-κB activity could be up-regulated when Lc-RIP3 is co-expressed with Lc-RIP1 or Lc-IRF7. These results collectively indicate that Lc-RIP3 acts as an important regulator in host innate immune signaling in teleosts.

PEGylated Graphene Oxide Carried OH-CATH30 to Accelerate the Healing of Infected Skin Wounds.

BACKGROUND: The treatment of Staphylococcus aureus (S. aureus)-infected wounds is difficult. It causes extreme pain to tens of thousands of patients and increases the cost of medical care. The antimicrobial peptide OH-CATH30 (OH30) has a good killing activity against S. aureus and can play a role in accelerating wound healing and immune regulation. Therefore, it shows great potential for wound healing. PURPOSE: The aim of this study was to overcome the short half-life and easy enzymolysis of OH30 by using graphene oxide conjugated with polyethylene glycol to load OH30 (denoted as PGO-OH30), as well as to evaluate its effect on wounds infected by S. aureus. METHODS: PGO-OH30 nanoparticles were prepared by π-π conjugation and characterized. Their cell cytotoxicity, cell migration, infectious full-thickness dermotomy models, and histopathology were evaluated. RESULTS: Characterization and cytotoxicity experiments revealed that the PGO-OH30 drug-delivery system had good biocompatibility and excellent drug-delivery ability. Cell-migration experiments showed that PGO-OH30 could promote the migration of human immortalized keratinocytes (HaCaT) cells compared with the control group (P<0.05). In a mouse model of skin wound infection, PGO-OH30 accelerated skin-wound healing and reduced the amount of S. aureus in wounds compared with the control group (P<0.05). In particular, on day 7, the number of S. aureus was 100 times lower in the PGO-OH30 group than in the control group. CONCLUSION: The PGO-OH30 drug-delivery system had good biocompatibility and excellent drug-delivery ability, indicating its good therapeutic effect on a skin wound-infection model.

Elements in potable groundwater in Rugao longevity area, China: Hydrogeochemical characteristics, enrichment patterns and health assessments.

Rugao city is a typical longevity area taking shallow groundwater as the primary drinking water source. To determine the relationship between longevity and groundwater conditions, the hydrogeochemical characteristics and related causes of potable groundwater were investigated. On this basis, the water quality index (WQI) and hazard index (HI) of groundwater were evaluated. Meanwhile, the nutrient indicators beneficial to human health, like Ca and Mg concentrations, were also considered to explore the relationship. The results were as following: (1) 91.3% of water samples fell under the Ca/Mg-HCO3 water type, which resulted from the dissolution of silicate rock. Na, Cl-, Br, B in groundwater emanated from seawater intrusion. The abnormal concentrations of NO3- and As also indicated that anthropogenic activities had exerted significant influences on groundwater quality. (2) The average WQI value was 30.19, which meant that the overall groundwater quality in Rugao city was pretty good. However, 8 water samples were found to have HI values above 1, which might be attributed to the high concentration of As (maximum value 0.0407 mg/L; mean value 0.0076 mg/L). In general, low WQI and HI values corresponded to towns with a high longevity population; what's more, WQI and HI values of Rugao city were lower than those of non-longevity areas. (3) Comparing with adjacent non-longevity areas, the potable groundwater in Rugao city had the characteristics of high Ca (mean value 123.57 mg/L), high Mg (mean value 50.33 mg/L) and high SO42- (mean value 525.19 mg/L). The daily intake of Ca and Mg from drinking water could meet 12.4% and 22.4% of daily Ca and Mg requirements, respectively. Also, the areas where the Sr and B concentrations were higher usually had higher life expectancy. The high concentrations of Ca, Mg, SO42-, Sr and B in drinking water, as well as low WQI and HI values, probably contribute to physical health and longevity. This research helps provide an insight into the relationship between groundwater quality and health and can serve as a reference for drinking water quality management.