Thioclava litoralis sp. nov., a novel species of alphaproteobacterium, isolated from surface seawater.

A Gram-negative, aerobic, rod-shaped, non-motile bacterium, designated as FTW29T, was isolated from surface seawater sampled in Futian district, Shenzhen, China. Growth of strain FTW29T was observed at 15-42 ℃ (optimum, 28-30 ℃), pH 4.0-9.0 (optimum, pH 5.5-7.5) and in the presence of 0.5-10% NaCl (optimum, 3.0% NaCl). Strain FTW29T showed 95.0-96.8% 16 S rRNA gene sequence similarity to various type strains of the genera Thioclava, Sinirhodobacter, Rhodobacter, Haematobacter and Frigidibacter of the family Paracoccaceae, and its most closely related strains were Thioclava pacifica DSM 10,166T (96.8%) and Thioclava marina 11.10-0-13T (96.7%). The phylogenomic tree constructed on the bac120 gene set showed that strain FTW29T formed a clade with the genus Thioclava, with a bootstrap value of 100%. The evolutionary distance values between FTW29T and type strains of the genus Thioclava were 0.17-0.19, which are below the recommended standard (0.21-0.23) for defining a novel genus in the family Paracoccaceae. In strain FTW29T, the major fatty acids identified were summed feature 8 (C18:1ω7c) and C16:0, and the predominant respiratory quinones were ubiquinone-10 and ubiquinone-9. The composition of polar lipids in strain FTW29T included diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, an unidentified phospholipid, an unidentified aminolipid, two unidentified glycolipids and an unidentified lipid. The genome of strain FTW29T comprised one circle chromosome and six plasmids, with a G + C content of 61.4%. The average nucleotide identity, average amino acid identity, and digital DNA-DNA hybridization values between strain FTW29T and seven type strains of the genus Thioclava were 76.6-78.4%, 53.2-56.4% and 19.3-20.4%, respectively. Altogether, the phenotypic, phylogenetic and chemotaxonomic evidence illustrated in this study suggested that strain FTW29T represents a novel species of the genus Thioclava, with the proposed name Thioclava litoralis sp. nov. The type strain is FTW29T (= KCTC 82,841T = MCCC 1K08523T).

Microbulbifer bruguierae sp. nov., isolated from sediment of mangrove plant Bruguiera sexangula, and comparative genomic analyses of the genus Microbulbifer.

A Gram-negative, non-motile, strictly aerobic, rod-shaped bacterium, designated as H12T, was isolated from the sediments of mangrove plant Bruguiera sexangula taken from Dapeng district, Shenzhen, PR China. The pairwise 16S rRNA gene sequence analysis showed that strain H12T shared high identity levels with species of the genus Microbulbifer, with the highest similarity level of 98.5 % to M. pacificus SPO729T, followed by 98.1 % to M. donghaiensis CN85T. Phylogenetic analysis using core-genome sequences showed that strain H12T formed a cluster with type species of M. pacificus SPO729T and M. harenosus HB161719T. The complete genome of strain H12T was 4 481 396 bp in size and its DNA G+C content was 56.7 mol%. The average nucleotide identity and digital DNA-DNA hybridization values among strain H12T and type species of genus Microbulbifer were below the cut-off levels of 95-96 and 70 %, respectively. The predominant cellular fatty acids of strain H12T were iso-C15 : 0 (22.5 %) and C18 : 1 ω7c (13.9 %). Ubiquinone-8 was detected as the major respiratory quinone. The polar lipids of strain H12T comprised one phosphatidylglycerol, one phosphatidylethanolamine, one unidentified aminoglycophospholipid, one unidentified glycophospholipid, three unidentified glycolipids, two unidentified aminolipids, and one unidentified lipid. Based on polyphasic evidence, strain H12T represents a novel species of the genus Microbulbifer, for which the name Microbulbifer bruguierae sp. nov. is proposed. The type strain is H12T (=KCTC 92859T=MCCC 1K08451T). Comparative genomic analyses of strain H12T with strains of the genus Microbulbifer reveal its potential in degradation of pectin.

Different activation of STAT1 and STAT2 phosphorylation by IFNc, IFNd, and IFNh in tilapia.

Type I IFNs are a subset of cytokines exerting their antiviral effects mainly through the JAK-STAT signalling. Immunogenetic studies have shown that fish possess key components of IFN-JAK-STAT cascade, but the information about the distinct responses of STAT1 and STAT2 to different IFNs is rather limited in fish. Here, we identified and cloned STAT1 and STAT2 genes (named as On-STAT1 and On-STAT2) from tilapia, Oreochromis niloticus. On-STAT1 and On-STAT2 genes were detected in all orangs/tissues examined, and were rapidly induced in spleen, head kidney, and liver following the stimulation of poly(I:C). In addition, the stimulation of poly(I:C), poly(A:T), and different subgroups of recombinant IFNs could induce the expression of On-STAT1 and On-STAT2 in TA-02 cells with distinct induction levels. Importantly, On-STAT2 was rapidly phosphorylated by all three subgroups of IFNs, but the phosphorylation of On-STAT1 was only observed in IFNc- and IFNh-treated TA-02 cells, reflecting the distinct activation of STAT by different subgroups of fish IFNs. The present results thus contribute to better understanding of the JAK-STAT signalling mediated by different subgroups of IFNs in fish.

[MMPs/pH synergically responsive XTS-Prussian blue nanoparticles inhibiting proliferation and migration of RAFLS assisted with laser irradiation].

Rheumatoid arthritis(RA) is a condition in which the joints are in a weakly acidic environment. In RA, RA fibroblastlike synoviocytes( RAFLS) in the joints become abnormally activated and secrete a large amount of matrix metalloproteinases(MMPs), and the receptor protein CD44 on the cell membrane is specifically upregulated. Xuetongsu(XTS), an active ingredient in the Tujia ethnomedicine Xuetong, is known to inhibit the proliferation of RAFLS. However, its development and utilization have been limited due to poor targeting ability. A biomimetic XTS-Prussian blue nanoparticles(PB NPs) drug delivery system called THMPX NPs which can target CD44 was constructed in this study. The surface of THMPX NPs was modified with hyaluronic acid(HA) and a long chain of triglycerol monostearate(TGMS) and 3-aminobenzeneboronic acid(PBA)(PBA-TGMS). The overexpressed MMPs and H+ in inflammatory RAFLS can synergistically cleave the PBA-TGMS on the surface of the nanoparticles, exposing HA to interact with CD44. This allows THMPX NPs to accumulate highly in RAFLS, and upon near-infrared light irradiation, generate heat and release XTS, thereby inhibiting the proliferation and migration of RAFLS. Characterization revealed that THMPX NPs were uniform cubes with a diameter of(190. 3±4. 7) nm and an average potential of(-15. 3± 2. 3) m V. Upon near-infrared light irradiation for 5 min, the temperature of THMPX NPs reached 41. 5 ℃, indicating MMPs and H+-triggered drug release. Safety assessments showed that THMPX NPs had a hemolysis rate of less than 4% and exhibited no cytotoxicity against normal RAW264. 7 and human fibroblast-like synoviocytes(HFLS). In vitro uptake experiments demonstrated the significant targeting ability of THMPX NPs to RAFLS. Free radical scavenging experiments revealed excellent free radical clearance capacity of THMPX NPs, capable of removing reactive oxygen species in RAFLS. Cell counting kit-8 and scratch assays demonstrated that THMPX NPs significantly suppressed the viability and migratory ability of RAFLS. This study provides insights into the development of innovative nanoscale targeted drugs from traditional ethnic medicines for RA treatment.

Copper and temperature shaped abundant and rare community assembly respectively in the Yellow River.

Untangling assembly and microbial interaction of abundant and rare microbiota in aquatic ecosystem is pivotal for understanding how community assembly respond to environmental variables and co-occurrence patterns. Here, we explored the assembly mechanisms, their drivers, and species co-occurrence of abundant and rare microbiomes in the Yellow River using 16S rRNA gene sequencing in Lanzhou, China. Here, abundant community was ubiquitous across all sites, whereas rare community was uneven distributed. The richness and community dissimilarity of rare taxa were significantly greater than those of abundant ones. Stochastic processes structured the rare community assembly in spring and winter, while deterministic processes shaped the abundant and rare community assembly in other seasons and all sites. Copper and water temperature mediated the balance between deterministic and stochastic processes of abundant and rare community, respectively. A few abundant taxa with closer relationships frequently occupied central positions and had a great effect on other co-occurrences in the network, while the majority of keystone microbiota were rare microbiome and played a considerable part in maintaining the network structure. Our study provides some ecological proposals for water quality management and ecological stability of the Yellow River. KEY POINTS: • Deterministic process dominated abundant and rare community assembly. • Cu and TW mediated the balance of abundant and rare community assembly respectively. • Abundant taxa had a greater effect on other co-occurrences in the network.

Description and genomic characterization of Gallaecimonas kandeliae sp. nov., isolated from the sediments of mangrove plant Kandelia obovate.

The genus Gallaecimonas, proposed by Rodríguez-Blanco et al. (Int J Syst Evol Microbiol 60:504-509, 2010), is mainly isolated from marine environments. So far, only three species have been identified and characterized in this genus. In this study, a new Gallaecimonas strain named Q10T was isolated from the sediments of mangrove plant Kandelia obovate taken from Dapeng district, Shenzhen, China. Strain Q10T was a Gram-stain-negative, non-motile, strictly aerobic, rod-shaped bacterium, and grew with 0-8.0% (w/v) NaCl, at 10-45 °C and at pH 5.5-8.5. Phylogenetic analysis indicated that strain Q10T and the three Gallaecimonas species formed a clade in the tree, with 16S rRNA gene sequence similarities ranging from 96.0 to 97.0%. The major respiratory quinone is Q8. The polar lipids comprised aminolipid, aminophospholipid, diphosphatidylglycerol, glycolipid, phosphatidylethanolamine, phosphatidylglycerol, glycophospholipid and phospholipid. The predominant fatty acids are C16:0, C17:1ω8c, summed feature 3 (C16:1ω7c/C16:1ω6c), and iso-C16:0. The complete genome of strain Q10T is 3,836,841 bp with a G+C content of 62.6 mol%. The orthologous proteins analysis revealed 55 unique proteins in strain Q10T related to important biological processes, especially three frataxins related to iron-sulfur cluster assembly, which may play a pivotal role in environmental adaptability of this species. Based on polyphasic taxonomic data, strain Q10T is considered to represent a novel species within the genus Gallaecimonas, for which the name Gallaecimonas kandelia sp. nov. is proposed. The type strain is Q10T (=KCTC 92860T=MCCC 1K08421T). These results contribute to a better understanding of general features and taxonomy of the genus Gallaecimonas.

Comparative genomic analysis provides insights into taxonomy and temperature adaption of Aeromonas salmonicida.

Aeromonas salmonicida has long been known as psychrophiles since it is mainly isolated from cold water fish, and recent reports have revealed the existence of mesophilic strains isolated from warm sources. However, the genetic differences between mesophilic and psychrophilic strains remain unclear due to few complete genomes of mesophilic strain are available. In this study, six A. salmonicida (2 mesophilic and 4 psychrophilic) were genome-sequenced, and comparative analyses of 25 A. salmonicida complete genomes were conducted. The ANI values and phylogenetic analysis revealed that 25 strains formed three independent clades, which were referred as typical psychrophilic, atypical psychrophilic and mesophilic groups. Comparative genomic analysis showed that two chromosomal gene clusters, related to lateral flagella and outer membrane proteins (A-layer and T2SS proteins), and insertion sequences (ISAs4, ISAs7 and ISAs29) were unique to the psychrophilic groups, while the complete MSH type IV pili were unique to the mesophilic group, all of which may be considered as lifestyle-related factors. The results of this study not only provide new insights into the classification, lifestyle adaption and pathogenic mechanism of different strains of A. salmonicida, but also contributes to the prevention and control of disease caused by psychrophilic and mesophilic A. salmonicida.

Molecular cloning, expression analysis and functional characterization of NEDD4 from Nile tilapia (Oreochromis niloticus).

Neural precursor cell-expressed developmentally downregulated gene 4 (NEDD4) was a member of HECT E3 ubiquitin ligases, which participated in various biological processes. In this study, a NEDD4 was identified and analyzed in Nile tilapia, Oreochromis niloticus (OnNEDD4) and its open reading frame was 2781 bp, encoding 926 amino acids. Three conserved structure features were found in OnNEDD4, including C2 domain, WW domains and HECT domain. OnNEDD4 was constitutively expressed in all examined tissues and the highest expression level was observed in thymus. After Streptococcus agalactiae stimulation, OnNEDD4 was significantly induced in several tissues, including thymus, intestine, blood and gill. Moreover, yeast two-hybrid assay shown OnNEDD4 could interact with extracellular region of OnCD40, but this interaction didn't affect the phagocytosis of monocytes/macrophages (MO/MΦ) to S. agalactiae and A. hydrophila. Taken together, the present study suggested that OnNEDD4 participate in CD40-mediated immune response excluding phagocytosis.

Characterization of TRAF2 in Nile tilapia: Expression profiles and the role in decreasing NF-κB pathway.

Mammals TRAF2 played a dual role in several immune signaling transduction processes. In this study, TRAF2 was cloned from Nile tilapia, Oreochromis niloticus, which named OnTRAF2. The open reading frame was 1797 bp, encoding 598 amino acids. Amino acid alignment and phylogenetic analysis indicated that OnTRAF2 showed relatively low identify with other teleost TRAF2 proteins, with the exception of TRAF2s from Epinephelus coioides. In healthy tilapia, OnTRAF2 was expressed widely in all the examined tissues, which had highest expression level in the brain. After Streptococcus agalactiae infection, the expression level of OnTRAF2 was increased significantly at different times in several organs, implying that OnTRAF2 may be involved in host defense against S. agalactiae infection. The result of subcellular localization showed that OnTRAF2 presented in cytoplasm and nucleus of HEK293T cells. Additionally, overexpression of OnTRAF2 significantly decreased the transcriptional activity of the NF-κB reporter in HEK293T cells, yeast two-hybrid results revealed that OnTRAF2 had no interaction with E3 ubiquitin ligase OnNEDD4. These results indicated that OnTRAF2 played important function during bacterial infection, and negatively mediated the immune signaling transduction in Nile tilapia, while the mechanism need further study.

CD40 induces an antimicrobial response against the intracellular pathogen Streptococcus agalactiae in Nile tilapia, Oreochromis niloticus.

Streptococcus agalactiae is a Gram-positive facultative intracellular bacterium that leads to severe economic loss of tilapia worldwide. Previous studies demonstrated that CD40 contributes to host protection against intracellular injection. In this study, CD40 was characterized from Nile tilapia (Oreochromis niloticus), named OnCD40. Sequence analysis showed that open reading frame of OnCD40 was 933 bp, containing a single peptide, a transmembrane domain and four cysteine-rich domains. The qRT-PCR revealed that OnCD40 was expressed in all examined tissues with the most abundant ones in spleen and thymus. After S. agalactiae stimulation, the expression of OnCD40 was significantly induced in most of the detected organs. Moreover, OnCD40-overexpressing fish elicited significant protection against subsequent S. agalactiae challenge; approximately 10000-fold fewer bacteria were detected in spleen of OnCD40-overexpressing fish in comparison with control fish. Thus, CD40 had protecting function in Nile tilapia against intracellular pathogens.

[Value of Diffusion-weighted Imaging and Apparent Diffusion Coefficient in the Differential Diagnosis of Posterior Fossa Solid Hemangioblastoma].

Objective To investigate the value of diffusion-weighted imaging(DWI)and apparent diffusion coefficient(ADC)in the diagnosis and differential diagnosis of posterior fossa solid hemangioblastoma(PFSH). Methods We retrospectively analyzed the clinical data of 15 PFSH patients and 58 patients with other hypervascular tumors in the posterior fossa(the latter included 23 cases of meningioma,5 cases of medulloblastoma,8 cases of acoustic neuroma,4 cases of hemangiopericytoma,5 cases of lymphoma,9 cases of metastatic tumor,3 cases of astrocytoma,and 1 case of choroid plexus papilloma)confirmed by operation and pathology.All patients underwent axial DWI scans,and the mean ADC value of solid part of the tumors and the adjacent normal cerebellar white matter were measured,and then the normalized ADC was calculated.In addition,t test was used to compare the differences in mean ADC and normalized ADC between these two groups,and receiver operating characteristic(ROC)curve was applied to analyze the diagnostic performance of normalized ADC. Results Of all the 15 PFSH patients,DWI appeared hypointense in 12 patients and isointense in 3 patients;the signals on ADC maps were isointense or hyperintense;the mean ADC value of PFSHs was(1.881±0.445)×10 -3mm 2/s and the normalized ADC was 2.70±0.62.In contrast,in 58 patients with other tumors in the posterior fossa,DWI appeared hyperintense in 51 cases,isointense in 3 cases,and hypointense in 4 cases;the mean ADC value was(0.771±0.202)×10 -3 mm 2/s,and the normalized ADC was 1.17±0.33.Thus,the ADC value and normalized ADC value were significantly higher in PFSH than in other tumors in the posterior fossa(t=9.419,P<0.001;t=9.184,P<0.001).The cut-off value of the normalized ADC for the diagnosis of solid hemangioblastoma was 1.89,with the sensitivity and specificity being 100%and 96.6%respectively,and the area under the ROC curve was 0.989. Conclusion ADC and normalized ADC are valuable in the differential diagnosis of PFSH from other tumors with abundant blood supply.

Efficient directional coupling from multilayer-graphene-based long-range SPP waveguide to metal-based hybrid SPP waveguide in mid-infrared range.

Graphene-based and metal-based surface plasmon polariton (SPP) waveguides have attracted intense research interest because they can be used as basic components to propagate electromagnetic (EM) waves in future optical integrated systems. We propose a directional coupler, which can couple EM energy from a multilayer-graphene-based cylindrical long-range SPP waveguide to a metal-based cylindrical hybrid SPP waveguide in the mid-infrared range. This coupler exhibits relatively low coupling length, high coupling efficiency, low insertion loss, and high extinction ratio after adjustment of the wave vector mismatch of the two waveguides. Moreover, this coupler is tolerant to practical fabrication errors like misalignment of graphene layres, and can effectively work in the range of Fermi energy Ef > 0.6 eV when the mobility of graphene varies from 10000 to 800 cm2/Vs. Hence, the coupler offers potential applications in signal routing and information exchange between graphene-based and metal-based SPP waveguides in photonic integrated circuits.

Dietary supplementation with selenium yeast and tea polyphenols improve growth performance and nitrite tolerance of Wuchang bream (Megalobrama amblycephala).

In order to explore the effects of dietary selenium yeast, tea polyphenols and their combination on growth of Wuchang bream (Megalobrama amblycephala) and its resistance to nitrite stress, 360 healthy Wuchang bream with initial body weight of (55.90 ± 2.60) g were randomly divided into four groups: a control group fed with basal diet and three treated groups fed with basal diets supplemented with 0.50 mg/kg selenium yeast, 50 mg/kg tea polyphenols, and the combination of 0.50 mg/kg selenium yeast and 50 mg/kg tea polyphenols, respectively. After 60 d of feeding, the growth performance of Wuchang bream was measured. Then 25 fish per tank were exposed to nitrite stress of 15.0 mg/L. The serum stress hormones, liver histology and hepatic antioxidant responses were evaluated before nitrite exposure (0 h) and at 6, 12, 24, 48 and 96 h after exposure. The results showed that before nitrite exposure, compared with the control, the weight gain, specific growth rate, liver total antioxidant capacity, the activities and transcriptional levels of hepatic antioxidant enzymes (superoxide dismutase and glutathione peroxidase) in the selenium yeast and combination groups were significantly increased, while feed conversion rate was decreased significantly, which suggested that the combined use of selenium yeast and tea polyphenols as well as the single selenium yeast supplementation improved growth performance and enhanced antioxidant capacity in fish. After nitrite exposure, compared with the control, liver total antioxidant capacity as well as the activities and transcription levels of catalase superoxide dismutase and glutathione peroxidase in three treatment groups were significantly increased in varying degrees whereas serum cortisol contents and liver malondialdehyde levels were decreased significantly. By contrast, the combined use of selenium yeast and tea polyphenols was more effective than the single supplementation with selenium yeast or tea polyphenols. In consistent with this, alterations of the liver histostructure in three treatment groups were slower and less severe than in the control group after nitrite exposure. In conclusion, a basal diet supplemented with the combination of 0.50 mg/kg selenium yeast and 50 mg/kg tea polyphenols could effectively improve growth performance and nitrite resistance in Wuchang bream.

Comparative analysis of the intestinal bacterial communities in different species of carp by pyrosequencing.

Gut microbiota is increasingly regarded as an integral component of the host, due to important roles in the modulation of the immune system, the proliferation of the intestinal epithelium and the regulation of the dietary energy intake. Understanding the factors that influence the composition of these microbial communities is essential to health management, and the application to aquatic animals still requires basic investigation. In this study, we compared the bacterial communities harboured in the intestines and in the rearing water of grass carp (Ctenopharyngodon idellus), crucian carp (Carassius cuvieri), and bighead carp (Hypophthalmichthys nobilis), by using 454-pyrosequencing with barcoded primers targeting the V4 to V5 regions of the bacterial 16S rRNA gene. The specimens of the three species were cohabiting in the same pond. Between 6,218 and 10,220 effective sequences were read from each sample, resulting in a total of 110,398 sequences for 13 samples from gut microbiota and pond water. In general, the microbial communities of the three carps were dominated by Fusobacteria, Firmicutes, Proteobacteria and Bacteroidetes, but the abundance of each phylum was significantly different between species. At the genus level, the overwhelming group was Cetobacterium (97.29 ± 0.46 %) in crucian carp, while its abundance averaged c. 40 and 60 % of the sequences read in the other two species. There was higher microbial diversity in the gut of filter-feeding bighead carp than the gut of the two other species, with grazing feeding habits. The composition of intestine microbiota of grass carp and crucian carp shared higher similarity when compared with bighead carp. The principal coordinates analysis (PCoA) with the weighted UniFrac distance and the heatmap analysis suggested that gut microbiota was not a simple reflection of the microbial community in the local habitat but resulted from species-specific selective pressures, possibly dependent on behavioural, immune and metabolic characteristics.

Theoretical study of the nonlinear magnon-phonon coupling in CoF2.

The coupling and interplay between magnon and phonon are important topics for spintronics and magnonics. In this work we studied the nonlinear magnon-phonon coupling in CoF2. First-principles calculations demonstrate that the antiferromagnetic resonance magnon drives a phonon with B1gcharacter; the oscillating driving force has a frequency twice of that of the magnon. Comparing with similar materials indicates a strong correlation between the strength of nonlinear magnon-phonon coupling and the orbital magnetic moment of the magnetic ion. This work pave the way for theoretical study of nonlinear magnon-phonon coupling.

Sustained-Release Hydrogen-Powered Bilateral Microneedles Integrating CD-MOFs for In Situ Treating Allergic Rhinitis.

Glucocorticoids are widely used for treating allergic rhinitis, but conventional intranasal administration encounters unfavorable nasal cilia clearance and nasal mucosal barrier. Herein, a bilateral microneedle patch is fabricated for delivering cyclodextrin-based metal-organic frameworks (CD-MOF) encapsulating dexamethasone (DXMS) and paeonol (Pae), while NaH particles are mounted on the basal part of each microneedle. By intranasal administration, the microneedles are propelled into the nasal mucosa by NaH-generated hydrogen and then swell to form a hydrogel for sustainedly releasing drugs. The DXMS/Pae combination is demonstrated to be superior to more than the twofold dose of DXMS alone for improving allergic rhinitis in rats. It involves reducing mast cell degranulation and modulating Treg/Th17 cell homeostasis, whereas inhibiting Th1 to Th2 differentiation is associated with regulating the GATA3/T-bet pathway, as well as repairing epithelial barrier function by increasing MUC1 and downregulating periostin. In addition, this delivery system modulates the lipid metabolism of the nasal mucosa. Notably, the newly designed device significantly enhances the drug's therapeutic effect, and NaH-generated hydrogen may have the potential adjunctive therapeutic effect. Collectively, such an emerging microneedle-mediated nasal drug delivery creates a new form for alleviating immune inflammation and contributes a promising solution to reduce clinical glucocorticoid abuse.

Identification and functional characterization of a long-type peptidoglycan recognition protein, PGRP-L in amphibian Xenopus laevis.

Peptidoglycan recognition proteins (PGRPs) are a family of multifunctional proteins playing vital roles in PGN metabolism and antibacterial defense, and their functions have been well-characterized in mammals, bony fishes, and insects. However, the information about the functions of amphibian long-type PGRP is rather limited. Here, we identified and cloned a long-type PGRP gene (named Xl-PGRP-L) from African clawed frog, Xenopus laevis. Xl-PGRP-L gene was detected in all orangs/tissues examined, and was rapidly induced in intestine, liver, and lung following the stimulation of PGN. Sequence analysis showed that Xl-PGRP-L possesses four Zn2+-binding residues (His358, Tyr395, His470, and Cys478) required for amidase activity of catalytic PGRPs, and assays for amidase activity revealed that recombinant Xl-PGRP-L cloud degrade PGN in a Zn2+-dependent manner, indicating that Xl-PGRP-L is belonging to catalytic PGRPs. In addition, Xl-PGRP-L have antibacterial activity against Gram-negative bacteria Edwardsiella tarda and Gram-positive bacteria Streptococcus agalactiae. The present investigation represents the first characterization regarding the biological activities of amphibian long-type PGRPs, thus contributes to a better understanding of the functions of tetrapod PGRPs and the molecular mechanisms of amphibian antibacterial defense.

Engineering Cardiac Tissue for Advanced Heart-On-A-Chip Platforms.

Cardiovascular disease is a major cause of mortality worldwide, and current preclinical models including traditional animal models and 2D cell culture models have limitations in replicating human native heart physiology and response to drugs. Heart-on-a-chip (HoC) technology offers a promising solution by combining the advantages of cardiac tissue engineering and microfluidics to create in vitro 3D cardiac models, which can mimic key aspects of human microphysiological systems and provide controllable microenvironments. Herein, recent advances in HoC technologies are introduced, including engineered cardiac microtissue construction in vitro, microfluidic chip fabrication, microenvironmental stimulation, and real-time feedback systems. The development of cardiac tissue engineering methods is focused for 3D microtissue preparation, advanced strategies for HoC fabrication, and current applications of these platforms. Major challenges in HoC fabrication are discussed and the perspective on the potential for these platforms is provided to advance research and clinical applications.

Advances and Prospects for Hydrogel-Forming Microneedles in Transdermal Drug Delivery.

Transdermal drug delivery (TDD) is one of the key approaches for treating diseases, avoiding first-pass effects, reducing systemic adverse drug reactions and improving patient compliance. Microneedling, iontophoresis, electroporation, laser ablation and ultrasound facilitation are often used to improve the efficiency of TDD. Among them, microneedling is a relatively simple and efficient means of drug delivery. Microneedles usually consist of micron-sized needles (50-900 µm in length) in arrays that can successfully penetrate the stratum corneum and deliver drugs in a minimally invasive manner below the stratum corneum without touching the blood vessels and nerves in the dermis, improving patient compliance. Hydrogel-forming microneedles (HFMs) are safe and non-toxic, with no residual matrix material, high drug loading capacity, and controlled drug release, and they are suitable for long-term, multiple drug delivery. This work reviewed the characteristics of the skin structure and TDD, introduced TDD strategies based on HFMs, and summarized the characteristics of HFM TDD systems and the evaluation methods of HFMs as well as the application of HFM drug delivery systems in disease treatment. The HFM drug delivery system has a wide scope for development, but the translation to clinical application still has more challenges.

Evolutionary and functional conservation of myeloid differentiation factor 88 (MyD88) in amphibian Xenopus tropicalis.

As a universal adaptor used by most TLR members, the myeloid differentiation factor 88 (MyD88) plays essential roles in TLR-mediated inflammatory response of invertebrate and vertebrate animals, and functional features of MyD88 remain largely unknown in amphibians. In this study, a MyD88 gene named Xt-MyD88 was characterized in the Western clawed frog (Xenopus tropicalis). Xt-MyD88 and MyD88 in other species of vertebrates share similar structural characteristics, genomic structures, and flanking genes, suggesting that MyD88 is structurally conserved in different phyla of vertebrates ranging from fish to mammals. Moreover, Xt-MyD88 was widely expressed in different organs/tissues, and was induced by poly(I:C) in spleen, kidney, and liver. Importantly, overexpression of Xt-MyD88 triggered a marked activation of both NF-κB promoter and interferon-stimulated response elements (ISREs), implying that it may be play important roles in inflammatory responses of amphibians. The research represents the first characterization on the immune functions of amphibian MyD88, and reveals considerable functional conservation of MyD88 in early tetrapods.