Salivary factor LTRIN from Aedes aegypti facilitates the transmission of Zika virus by interfering with the lymphotoxin-ß receptor.

Pathogens have co-evolved with mosquitoes to optimize transmission to hosts. Mosquito salivary-gland extract is known to modulate host immune responses and facilitate pathogen transmission, but the underlying molecular mechanisms of this have remained unknown. In this study, we identified and characterized a prominent 15-kilodalton protein, LTRIN, obtained from the salivary glands of the mosquito Aedes aegypti. LTRIN expression was upregulated in blood-fed mosquitoes, and LTRIN facilitated the transmission of Zika virus (ZIKV) and exacerbated its pathogenicity by interfering with signaling through the lymphotoxin-ß receptor (LTßR). Mechanically, LTRIN bound to LTßR and 'preferentially' inhibited signaling via the transcription factor NF-κB and the production of inflammatory cytokines by interfering with the dimerization of LTßR during infection with ZIKV. Furthermore, treatment with antibody to LTRIN inhibited mosquito-mediated infection with ZIKV, and abolishing LTßR potentiated the infectivity of ZIKV both in vitro and in vivo. This study provides deeper insight into the transmission of mosquito-borne diseases in nature and supports the therapeutic potential of inhibiting the action of LTRIN to disrupt ZIKV transmission.

Investigation of a novel biofilm model close to the original oral microbiome.

A more optimized culture medium used in vitro to mimic the bacterial composition of original oral flora as similar as possible remains difficult at present, and the goal of this study is to develop a novel oral biofilm medium to restore the original oral microbiome. Firstly, we conducted a systematic literature review by searching PubMed and summarized the current reported culture media in vitro. Seven culture media were found. We used mixed saliva as the origin of oral species to compare the effects of the above media in culturing oral multispecies biofilms. Results indicated that among the seven media brain heart infusion containing 1% sucrose (BHIs) medium, PG medium, artificial saliva (AS) medium, and SHI medium could obviously gain large oral biofilm in vitro. The nutrients contained in different culture media may be suitable for the growth of different oral bacteria; therefore, we optimized several novel media accordingly. Notably, results of crystal violet staining showed that the biofilm cultured in our modified artificial saliva (MAS) medium had the highest amount of biofilm biomass. 16S rRNA gene sequencing showed that the operational taxonomic units (OTUs) and Shannon index of biofilm cultured in MAS medium were also the highest among all the tested media. More importantly, the 16S rRNA gene sequencing analysis indicated that the biofilm cultured in MAS medium was closer to the original saliva species. Besides, biofilm cultured by MAS was denser and produced more exopolysaccharides. MAS supported stable biofilm formation on different substrata. In conclusion, this study demonstrated a novel MAS medium that could culture oral biofilm in vitro closer to the original oral microbiome, showing a good application prospect. KEY POINTS: • We compare the effects of different media in culturing oral biofilms • A novel modified artificial saliva (MAS) medium was obtained in our study • The MAS medium could culture biofilm that was closer to oral microbiome.

Performance of Double-Arm Digital Subtraction Angiography (DSA)-Guided and C-Arm-Guided Percutaneous Kyphoplasty (PKP) to Treat Senile Osteoporotic Vertebral Compression Fractures.

BACKGROUND Osteoporotic vertebral compression fracture (OVCF) is a common fracture in the elderly. Conservative treatment requires prolonged bedding, which may lead to serious complications. To explore optimized use of percutaneous kyphoplasty (PKP) in the treatment of senile osteoporotic thoracolumbar vertebral compression fractures, in this study, we used C-arm-guided and double-arm digital subtraction angiography (DSA)-guided PKP to treat OVCF in elderly patients and analyzed the effective recovery. MATERIAL AND METHODS In all, 60 patients who presented with osteoporotic vertebral compression fractures at our hospital between July 2017 and February 2019 were analyzed. They were randomly divided into C-arm-guided group and the double-arm DSA-guided groups. Both groups were treated with percutaneous kyphoplasty. RESULTS A pain VAS score analysis revealed that there was no significant difference between the two groups before surgery (P>0.05). After surgery, the VAS scores showed a significant difference between the C-arm-guided group and the double-arm DSA-guided PKP treatment group (P<0.01). Moreover, with respect to the bone cement dosage, vertebral correction height, operation time, cumulative radiation dose, percolation rate, and volume of bone cement, the double-arm DSA-guided PKP treatment showed significantly better results than the C-arm-guided PKP treatment (P<0.01). CONCLUSIONS Our data revealed that double-arm DSA-guided PKP was more accurate in treatment of senile osteoporotic thoracolumbar vertebral compression fractures, producing excellent performance with more accurate intraoperative evaluation, shorter operative time, lower incidence of bone cement leakage, less intraoperative radiation dose, and higher safety, and thus, could be extensively applied to clinical surgery.

A One-Pot Polymerization for Concurrently Inducing Predominant Helicity in Optically Inactive Helical Polymer and Constructing Graphene-Based Chiral Hybrid Foams.

Synthetic chiral helical polymers have achieved impressive progress in past few decades. Unfortunately, how to construct chiral helical polymer-derived functional materials still remains highly challenging. The present contribution reports an unprecedented, one-step strategy for judiciously combining chiral helical polymer with graphene to construct chiral hybrid foams. Graphene oxide (GO), ascorbic acid (L-AA), Rh catalyst, and an achiral acetylenic monomer bearing phenylboronic acid group are mixed in an aqueous dispersion. Under mild conditions, the monomer underwent polymerization; meanwhile GO transforms into reduced graphene oxide (RGO) which in situ self-assembles to construct a 3D porous structure. Herein, L-AA simultaneously plays double roles: 1) working as a chiral source for the monomer to undergo helix-sense-selective polymerization or transferring its chirality to the polymer chains via forming borate structure; and 2) working as a reducing agent for reducing GO. The preparation strategy combines four processes into one single step: monomer polymerization, chirality transfer, reduction of GO, and RGO's self-assembly. The eventually obtained chiral hybrid foams demonstrate advantages of porous structure, chirality, and reversible borate functional groups. The established preparation strategy promises a potent platform for conveniently constructing advanced chiral polymeric materials and even chiral hybrids starting from achiral monomers.

A New Species of Pristionchus (Rhabditida: Diplogastridae) and Its Bacterial Symbiont from Yixing, China.

A new nematode species, Pristionchus entomophilus n. sp., was collected during a soil sample survey in Yixing of Jiangsu province, eastern China. P. entomophilus n. sp. is distinguished by its unique characteristics. This new species is mainly hermaphroditic, with males seldom found. The new nematode has a similar body length but has much narrower body width compared with P. pacificus. Its body is covered with longitudinal ridges: 12 ridges on head, 13 or 14 ridges in the middle, 11 and 7 ridges in front and rear of the anus, respectively. The eurystomatous form mouth includes a triangular dorsal tooth, a large claw-like right subventral tooth, and a row of five ventral denticles placed opposite the dorsal tooth. Only eight pairs of genital papillae and a pair of phasmids are present in the tail of the male as the sixth pair of papillae having seemingly been degenerated and lost. Molecular phylogenetic trees based on 18S rDNA confirmed that the new species belongs to the genus Pristionchus and is most closely related to P. pacificus. Moreover, the new species was found to be occasionally associated with the entomopathogenic bacterial strain 09FLYB1 of Serratia nematodophila and be able to stably transfer the bacterial strain for several generations.

Streptococcus mutans membrane vesicles inhibit the biofilm formation of Streptococcus gordonii and Streptococcus sanguinis.

Streptococcus mutans, whose main virulence factor is glucosyltransferase (Gtf), has a substantial impact on the development of dental caries. S. mutans membrane vesicles (MVs), which are rich in Gtfs, have been shown to affect biofilm formation of other microorganisms. Streptococcus gordonii and Streptococcus sanguinis are initial colonizers of tooth surfaces, which provide attachment sites for subsequent microorganisms and are crucial in the development of oral biofilms. S. mutans and S. gordonii, as well as S. mutans and S. sanguinis, have a complex competitive and cooperative relationship, but it is unclear whether S. mutans MVs play a role in these interspecific interactions. Therefore, we co-cultured S. mutans MVs, having or lacking Gtfs, with S. gordonii and S. sanguinis. Our results showed that S. mutans MVs inhibited biofilm formation of S. gordonii and S. sanguinis but did not affect their planktonic growth; contrastingly, S. mutans ΔgtfBC mutant MVs had little effect on both their growth and biofilm formation. Additionally, there were fewer and more dispersed bacteria in the biofilms of the S. mutans MV-treated group than that in the control group. Furthermore, the expression levels of the biofilm-related virulence factors GtfG, GtfP, and SpxB in S. gordonii and S. sanguinis were significantly downregulated in response to S. mutans MVs. In conclusion, the results of our study showed that S. mutans MVs inhibited biofilm formation of S. gordonii and S. sanguinis, revealing an important role for MVs in interspecific interactions.

Polyvinyl alcohol/sodium alginate composite sponge with 3D ordered/disordered porous structure for rapidly controlling noncompressible hemorrhage.

It is still a challenge to develop a sponge that can efficiently control noncompressible bleeding to meet the emergency treatment and clinical demand. Herein, we combined the 3D printing sacrificial template method and freeze-drying technology to prepare polyvinyl alcohol/sodium alginate (PVA/SA) composite sponges with ordered microchannels and disordered porous structure. Compared with conventional sponges, the prepared sponge showed ultra-rapid water/blood absorption capacity and satisfactory mechanical properties. Furthermore, when the sponge was stuffed into a noncompressible wound and contacted with blood, it could accurately guide and quickly absorb a large amount of blood through the microchannels. Moreover, the platelets, red blood cells and coagulation factors would be enriched in the microchannels and microporous structure. In the SD rat liver noncompressible hemorrhage and femoral artery puncture injury model, PVA-SA composite sponge with 3D ordered/disordered porous structure showed enhanced hemostatic performance compared with commercial MPVA sponges. Depend on the special ordered/disordered porous structure, PVA-SA composite sponge could accelerate the blood convergence and promote coagulation. This design of special porous structure opened up a new avenue to develop hemostatic sponges for rapidly controlling noncompressible hemorrhage.

Fabricating poly(vinyl alcohol)/gelatin composite sponges with high absorbency and water-triggered expansion for noncompressible hemorrhage and wound healing.

It is challenging for traditional hemostatic sponges to control massive and noncompressible hemorrhages in the military field and accidental trauma. In this work, a series of highly fluid-absorbent composite sponges with rapid expansion ability based on norbornene anhydride-modified poly(vinyl alcohol) and gelatin (PVA@Gel-Sps) were developed by a foaming technique, chemical and physical crosslinking reactions and lyophilization. The prepared PVA@Gel-Sp2 exhibited a 3500% maximum water absorption ratio with a fast water absorption speed, which was suitable for blood component concentration. Owing to its interconnected macroporous structure, robust mechanical strength and high resilience, the compressed sponge could rapidly re-expand to more than 10 times its volume in response to water and blood. Moreover, due to the synergistic effect of the PVA-based sponge and gelatin, PVA@Gel-Sp2 could obviously shorten the hemostasis time and reduce blood loss in SD rat liver defect noncompressible hemorrhage models, and exhibited better wound healing effects in a full-thickness skin defect model than commercial sponges. These results suggest that PVA@Gel-Sp2 is a potential candidate for controlling noncompressible hemorrhage and promoting wound healing.

Chemo-enzymatic synthesis, characterization, in vitro antioxidant capacity and oxidative stability studies of novel phosphatidylcholines with ω-3/ω-6 PUFAs and phenolic acids.

Novel phosphatidylcholines containing PUFAs and phenolic acids were synthesized from egg phosphatidylcholine (PC), PUFAs (docosahexaenoic, arachidonic and linoleic acids) and phenolic acids (caffeic, ferulic and p-coumaric acids) as substrates. The structures of modified PCs were confirmed by spectral analysis and were evaluated for antioxidant activities. The modified PCs containing caffeic and ferulic acids exhibited excellent antioxidant activities compared with butylated hydroxytoluene (BHT) and α-tocopherol. The synthesized compounds were also evaluated for the oxidative stabilities in liposome and organic solvent. The modified PCs showed more oxidative stable compared with standard PUFA-PCs and PUFA-PCs + BHT. Results showed that the oxidative stability decreased with increasing degree of unsaturation in organic solvent whereas in liposomes, increased with increasing degree of unsaturation due to tight packed configuration. In this study, phenolic acids were found to render protections for PUFAs in modified PCs from oxidation. Modified PCs may have great potential for applications in food, cosmetic and pharmaceutical industries.

Polysaccharide Based Hemostatic Strategy for Ultrarapid Hemostasis.

Bleeding complications usually cause significant morbidity and mortality in civilian and military populations. In clinical application, hemostatic sponges, gauzes, hydrogel, and bandages are widely used as the traditional effective hemostatic products for hemorrhage. However, the traditional hemostatic devices or agents cannot meet the requirement for treatment of massive bleeding. Therefore, the excellent hemostatic performance of hemostatic products are of great significance for saving lives. Natural polysaccharides, as the main chemical component, have been widely used in the preparation of hemostasis due to their perfect biocompatibility and biodegradability. Polysaccharide based hemostatic products are available in variety of forms, such as, hydrogel, sponges, gauze and microspheres. The purpose of the present review is to report the research progress on polysaccharide hemostatic products and technology.

Interaction of Hsp90AA1 with phospholipids stabilizes membranes under stress conditions.

During heat shock conditions, structural changes in cellular membranes may lead to cell death. Hsp90AA1 and other heat shock proteins involved in membranes are responsible for protecting membrane stabilization. However, the membrane binding mechanism of Hsp90AA1 remains largely uncharacterized. In this study, we showed Hsp90AA1 interacts with phospholipid membrane with high affinity. Using the depth-dependent fluorescence-quenching with brominated lipids, we found Hsp90AA1 penetrated 10.7 Šinto the hydrocarbon core of the lipid bilayer. Circular dichroism spectra studies showed Hsp90AA1 lost part of its α-helical structures upon interaction with phospholipid membrane. By assessing binding properties of the three Hsp90AA1 domains, we found Hsp90AA1 interacted into the lipid bilayer mainly toward its C-terminus domain (CTD). Using scanning electron microscopy, we examined the protection on host cell membrane by overexpressing Hsp90AA1. The results indicated Hsp90AA1 or Hsp90AA1-CTD expressing E. coli cells exhibited better membrane integrity compared to the control after thermal treatment. The following liposome leakage assay suggested the protection of Hsp90AA1 might due to its stabilization of the membrane lipid. Collectively, the present study demonstrates Hsp90AA1 embeds into the lipid bilayer through its C-terminal domain and the Hsp90AA1-lipid association potentially has a significant function in keeping membranes stabilization during stress conditions.

Simultaneous p-nitrophenol and nitrogen removal in PNP wastewater treatment: Comparison of two integrated membrane-aerated bioreactor systems.

The chemical p-nitrophenol (PNP) is a priority pollutant, and PNP wastewater is highly toxic and resistant to biodegradation. The traditional physical and chemical methods (adsorption, extraction, and oxidation) for treating PNP wastewater have the disadvantages of complicated processes, high costs and secondary pollution generation. In this study, two integrated membrane-aerated bioreactor systems (RA and RB) with anoxic and aerated zones were constructed to enhance PNP biodegradation. The results showed that a helical silicone rubber membrane module displayed a high oxygen supply rate under a low membrane aeration pressure, and the hydraulic flow state of the reactor approached ideal mixing. At an influent PNP concentration of 500 mg/L, the average removal rates of PNP, chemical oxygen demand (COD) and total nitrogen (TN) reached 95.86%, 89.77%, and 94.81%, respectively, for RA and 89.48%, 74.26% and 64.78%, respectively, for RB, indicating efficient simultaneous PNP and nitrogen removal. Compared with that of RB, the pre-anoxic zone in RA not only performed detoxification pretreatment but also enhanced PNP degradation and denitrification effects, which relieved the biological treatment burden of the subsequent aerated zone. Based on these comprehensive analyses of reactor performance, the hydroquinone pathway might be the main route in the aerobic degradation of PNP.

Effect of heat shock protein 90 against ROS-induced phospholipid oxidation.

The antioxidative role of Hsp90 purified from duck muscle on phospholipid was investigated in this study. Lipid oxidation was assessed by ferric thiocyanate method, and particle size, zeta potential measurements and transmission electron microscopy were employed to detect physical and chemical changes during oxidation of liposomes. Increase of the peroxidation products, decrease of the particle size and disruption of the spherical unity of the liposomes were detected when liposome was exposed to hydrogen peroxide (H2O2) oxidation, and Hsp90 was shown to protect liposome against oxidation. To further test the protection of Hsp90 on cell membrane, the Hsp90 transformed E. coli cell model was built. The Hsp90-containing E. coli showed higher survival and better membrane integrity as compared to the control upon H2O2 exposure. It is expected that Hsp90 plays an important role in the prevention of phospholipids oxidation in meat and has potential use as a food antioxidant.

Interaction of heat shock protein 90 B1 (Hsp90B1) with liposome reveals its potential role in protection the integrity of lipid membranes.

Heat shock proteins of 90kDa (Hsp90) are molecular chaperones essential for protein homeostasis. Besides chaperone activity, Hsp90 exhibits other cellular functions at membranes, yet how it interacts with membranes remains elusive. We report here that Hsp90B1 interacts with phospholipid membranes. We first cloned the full-length open reading frame of Hsp90B1 from Anas platyrhnchos (ApHsp90B1), and the gene was then heterologously expressed and purified. SPR analysis show the purified ApHsp90B1 interacts with phospholipid membranes with high affinity (KD 176±25nM), and the interaction occurs over a wide range of pH, which is especially distinct under acidic conditions. Tryptophan fluorescence and far-UV CD spectra studies find that the interaction of ApHsp90B1 with phospholipid membrane induces microenvironment changes of tryptophan residues and conformational change of some regions in ApHsp90B1, which might be the reason of its increased ATPase activity upon addition phospholipid vesicles. Importantly, the interaction of ApHsp90B1 with phospholipid vesicles significantly reduces lipolysis of the membrane phospholipid, suggesting that the interaction of Hsp90B1 with membrane could preserve membrane integrity. The present study therefore demonstrates for the first time that Hsp90B1 exhibits high affinity for phospholipid membrane and suggest Hsp90B1 play an important role in membrane-stabilizing via its interaction with membrane phospholipids.