Neural correlates of novelty detection in the primary auditory cortex of behaving monkeys.

The neural mechanisms underlying novelty detection are not well understood, especially in relation to behavior. Here, we present single-unit responses from the primary auditory cortex (A1) from two monkeys trained to detect deviant tones amid repetitive ones. Results show that monkeys can detect deviant sounds, and there is a strong correlation between late neuronal responses (250-350 ms after deviant onset) and the monkeys' perceptual decisions. The magnitude and timing of both neuronal and behavioral responses are increased by larger frequency differences between the deviant and standard tones and by increasing the number of standard tones preceding the deviant. This suggests that A1 neurons encode novelty detection in behaving monkeys, influenced by stimulus relevance and expectations. This study provides evidence supporting aspects of predictive coding in the sensory cortex.

Evaluation of the TLR3 involvement during Schistosoma japonicum-induced pathology.

BACKGROUND: Despite the functions of TLRs in the parasitic infections have been extensively reported, few studies have addressed the role of TLR3 in the immune response to Schistosoma japonicum infections. The aim of this study was to investigate the properties of TLR3 in the liver of C57BL/6 mice infected by S. japonicum. METHODS: The production of TLR3+ cells in CD4+T cells (CD4+CD3+), CD8+T cells (CD8+CD3+), γδT cells (γδTCR+CD3+), NKT cells (NK1.1+CD3+), B cells (CD19+CD3-), NK (NK1.1-CD3+) cells, MDSC (CD11b+Gr1+), macrophages (CD11b+F4/80+), DCs (CD11c+CD11b+) and neutrophils (CD11b+ Ly6g+) were assessed by flow cytometry. Sections of the liver were examined by haematoxylin and eosin staining in order to measure the area of granulomas. Hematological parameters including white blood cell (WBC), red blood cell (RBC), platelet (PLT) and hemoglobin (HGB) were analyzed. The levels of ALT and AST in the serum were measured using biochemical kits. The relative titers of anti-SEA IgG and anti-SEA IgM in the serum were measured by enzyme-linked immunosorbent assay (ELISA). CD25, CD69, CD314 and CD94 molecules were detected by flow cytometry. RESULTS: Flow cytometry results showed that the expression of TLR3 increased significantly after S. japonicum infection (P < 0.05). Hepatic myeloid and lymphoid cells could express TLR3, and the percentages of TLR3-expressing MDSC, macrophages and neutrophils were increased after infection. Knocking out TLR3 ameliorated the damage and decreased infiltration of inflammatory cells in infected C57BL/6 mouse livers.,The number of WBC was significantly reduced in TLR3 KO-infected mice compared to WT-infected mice (P < 0.01), but the levels of RBC, platelet and HGB were significantly increased in KO infected mice. Moreover, the relative titers of anti-SEA IgG and anti-SEA IgM in the serum of infected KO mice were statistically decreased compared with the infected WT mice. We also compared the activation-associated molecules expression between S.japonicum-infected WT and TLR3 KO mice. CONCLUSIONS: Taken together, our data indicated that TLR3 played potential roles in the context of S. japonicum infection and it may accelerate the progression of S. japonicum-associated liver pathology.

Characteristics of splenic PD-1+ γδT cells in Plasmodium yoelii nigeriensis infection.

Although the functions of programmed death-1 (PD-1) on αß T cells have been extensively reported, a role for PD-1 in regulating γδT cell function is only beginning to emerge. Here, we investigated the phenotypic and functional characteristics of PD-1-expressing γδT cells, and the molecular mechanism was also explored in the Plasmodium yoelii nigeriensis (P. yoelii NSM)-infected mice. Flow cytometry and single-cell RNA sequencing (scRNA-seq) were performed. An inverse agonist of RORα, SR3335, was used to investigate the role of RORα in regulating PD-1+ γδT cells. The results indicated that γδT cells continuously upregulated PD-1 expression during the infection period. Higher levels of CD94, IL-10, CX3CR1, and CD107a; and lower levels of CD25, CD69, and CD127 were found in PD-1+ γδT cells from infected mice than in PD-1- γδT cells. Furthermore, GO enrichment analysis revealed that the marker genes in PD-1+ γδT cells were involved in autophagy and processes utilizing autophagic mechanisms. ScRNA-seq results showed that RORα was increased significantly in PD-1+ γδT cells. GSEA identified that RORα was mainly involved in the regulation of I-kappaB kinase/NF-κB signaling and the positive regulation of cytokine production. Consistent with this, PD-1-expressing γδT cells upregulated RORα following Plasmodium yoelii infection. Additionally, in vitro studies revealed that higher levels of p-p65 were found in PD-1+ γδT cells after treatment with a RORα selective synthetic inhibitor. Collectively, these data suggest that RORα-mediated attenuation of NF-κB signaling may be fundamental for PD-1-expressing γδT cells to modulate host immune responses in the spleen of Plasmodium yoelii nigeriensis-infected C57BL/6 mice, and it requires further investigation.

Isolation of Enterococcus faecium and determination of its mechanism for promoting the growth and development of Drosophila.

Intestinal symbiotic microorganisms have a strong capacity to regulate the physiological functions of their host, and Drosophila serves as a useful model. Enterococcus faecium (E. faecium) is a member of the normal intestinal flora of animals. Lactic acid bacteria (LAB) such as E. faecium can promote the growth and development of Drosophila, but the mechanism of regulation of Drosophila is poorly understood. In this study, we found that E. faecium used a carbon source to produce probiotic acids. E. faecium is a symbiotic bacterium for Drosophila, and adult flies passed on parental flora to offspring. E. faecium promoted the growth and development of Drosophila, especially under poor nutritional conditions. E. faecium shortened the developmental process for Drosophila and accelerated the transformation from larva to pupa. Finally, E. faecium promoted the growth and development of Drosophila through TOR and insulin signalling pathways.

Immunological characteristics of CD103+CD8+ Tc cells in the liver of C57BL/6 mouse infected with plasmodium NSM.

CD103 is an important marker of tissue-resident memory T cells (TRM) which play important roles in fighting against infection. However, the immunological characteristics of CD103+ T cells are not thoroughly elucidated in the liver of mouse infected with Plasmodium. Six- to eight-week-old C57BL/6 mice were infected with Plasmodium yoelii nigeriensis NSM. Mice were sacrificed on 12-16 days after infection and the livers were picked out. Sections of the livers were stained, and serum aspartate aminotransferase (AST) and alanine transaminase (ALT) levels were measured. Moreover, lymphocytes in the liver were isolated, and the expression of CD103 was determined by using qPCR. The percentage of CD103 on different immune cell populations was dynamically observed by using flow cytometry (FCM). In addition, the phenotype and cytokine production characteristics of CD103+CD8+ Tc cell were analyzed by using flow cytometry, respectively. Erythrocyte stage plasmodium infection could result in severe hepatic damage, a widespread inflammatory response and the decrease of CD103 expression on hepatic immune cells. Only CD8+ Tc and γδT cells expressed higher levels of CD103 in the uninfected state.CD103 expression in CD8+ Tc cells significantly decreased after infection. Compared to that of CD103- CD8+ Tc cells, CD103+ CD8+ Tc cells from the infected mice expressed lower level of CD69, higher level of CD62L, and secreted more IL-4, IL-10, IL-17, and secreted less IFN-γ. CD103+CD8+ Tc cells might mediate the hepatic immune response by secreting IL-4, IL-10, and IL-17 except IFN-γ in the mice infected with the erythrocytic phase plasmodium, which could be involved in the pathogenesis of severe liver damage resulted from the erythrocytic phase plasmodium yoelii nigeriensis NSM infection.

TLR7 modulates extramedullary splenic erythropoiesis in P. yoelii NSM-infected mice through the regulation of iron metabolism of macrophages with IFN-γ.

Splenomegaly is a prominent clinical manifestation of malaria and the causes remain incompletely clear. Anemia is induced in malaria and extramedullary splenic erythropoiesis is compensation for the loss of erythrocytes. However, the regulation of extramedullary splenic erythropoiesis in malaria is unknown. An inflammatory response could facilitate extramedullary splenic erythropoiesis in the settings of infection and inflammation. Here, when mice were infected with rodent parasites, Plasmodium yoelii NSM, TLR7 expression in splenocytes was increased. To explore the roles of TLR7 in splenic erythropoiesis, we infected wild-type and TLR7 -/- C57BL/6 mice with P. yoelii NSM and found that the development of splenic erythroid progenitor cells was impeded in TLR7 -/- mice. Contrarily, the treatment of the TLR7 agonist, R848, promoted extramedullary splenic erythropoiesis in wild-type infected mice, which highlights the implication of TLR7 on splenic erythropoiesis. Then, we found that TLR7 promoted the production of IFN-γ that could enhance phagocytosis of infected erythrocytes by RAW264.7. After phagocytosis of infected erythrocytes, the iron metabolism of RAW264.7 was upregulated, evidenced by higher iron content and expression of Hmox1 and Slc40a1. Additionally, the neutralization of IFN-γ impeded the extramedullary splenic erythropoiesis modestly and reduced the iron accumulation in the spleen of infected mice. In conclusion, TLR7 promoted extramedullary splenic erythropoiesis in P. yoelii NSM-infected mice. TLR7 enhanced the production of IFN-γ, and IFN-γ promoted phagocytosis of infected erythrocytes and the iron metabolism of macrophages in vitro, which may be related to the regulation of extramedullary splenic erythropoiesis by TLR7.

In-situ compatibilized starch/polyacylonitrile composite fiber fabricated via dry-wet spinning technique.

An in-situ compatibilized starch (St) and polyacrylonitrile (PAN) composite spinning solution was designed by preparing starch-graft-polyacrylonitrile (St-g-PAN) through graft copolymerizing acrylonitrile from soluble starch and using ammonium cerium nitrate (CAN) as initiator. As dimethyl sulfoxide (DMSO) was used as the solvent, St/St-g-PAN/PAN/DMSO spinning solution was prepared and St/St-g-PAN/PAN composite fibers were obtained by dry-wet spinning technique. The effects of air gap, coagulation bath, hot drawing and stretching, and thermal-setting process were studied in detail. Fourier transform infrared spectroscopy (FT-IR), solid state nuclear magnetic resonance (13C NMR), thermogravimetric analysis (TGA), X-ray diffraction analysis (XRD), and scanning electron microscopy (SEM) were used to characterize the structure and morphology of the copolymer and the fibers. Single fiber strength tester and sonic orientation instrument were performed to measure the fiber mechanical properties and orientation degrees. The results showed that as the grafting ratio ~150.0% and the reacting mixture containing St ~9.8%, St-g-PAN ~81.6%, and homo-PAN ~8.6% in DMSO solution with 6.0 wt% in concentration were used, the spinning parameters such as air gap ~35 mm, coagulation bath concentration ~70%, temperature ~25 °C, and positive stretching ~48%, hot drawing and stretching 6 times at 80 °C, thermal-setting at 90 °C for 3 h under constant length mode were met, composite fibers with breaking strength 3.41 cN·dtex-1, breaking elongation 14.41%, sonic orientation factor 0.625, moisture recovery ratio 10.53% under standard condition (1 atm, 22 °C, and relative humidity 65%), and boiling water shrinkage ratio 9.60% were obtained. The as prepared composite fiber was better than common viscose fiber 2.11 cN·dtex-1 and cotton fiber ~3.24 cN·dtex-1 and expected to be used in the fields of medical gauze, bandage, protective clothing, et al. besides of common textiles. The in-situ compatibilization method can be applied in preparation of other composite polymer materials.

Cross-Modal Interaction and Integration Through Stimulus-Specific Adaptation in the Thalamic Reticular Nucleus of Rats.

Stimulus-specific adaptation (SSA), defined as a decrease in responses to a common stimulus that only partially generalizes to other rare stimuli, is a widespread phenomenon in the brain that is believed to be related to novelty detection. Although cross-modal sensory processing is also a widespread phenomenon, the interaction between the two phenomena is not well understood. In this study, the thalamic reticular nucleus (TRN), which is regarded as a hub of the attentional system that contains multi-modal neurons, was investigated. The results showed that SSA existed in an interactive oddball stimulation, which mimics stimulation changes from one modality to another. In the bimodal integration, SSA to bimodal stimulation was stronger than to visual stimulation alone but similar to auditory stimulation alone, which indicated a limited integrative effect. Collectively, the present results provide evidence for independent cross-modal processing in bimodal TRN neurons.

Study on polysaccharide polyelectrolyte complex and fabrication of alginate/chitosan derivative composite fibers.

Sodium alginate (SA) blending with quaternary ammonium chitosan (QAC) polysaccharide polyelectrolyte complex (PEC) system was chosen to research the binary blending of anionic and cationic polyelectrolytes in detail and to fabricate SA/QAC composite fibers. The potential charge and the rheology of the PEC solution were characterized through Zeta Laser Particle Size Analyzer and DV-C Rotary Rheometer, the structure and properties of the composite fiber were examined by FT-IR, XRD, SEM, EDS, and YG004 single fiber strength meter. The results showed that as the mass ratio of SA to QAC increased from 0/1 to 10/1, the state of the binary solution in water changed from transparent uniform solution to turbid solution with flocculent precipitate, then back to uniform solution, accompanied by the electrical potential change. Moreover, the electrical potential also depended on salt in solution. By using this uniform PEC solution with the mass ratio of SA to QAC 10/1 and concentration 5.5 wt% in water, SA/QAC composite fibers with excellent performances of breaking strength 2.37 cN·dtex-1 and breaking elongation 14.11%, good antibacterial and hydrophobic properties were fabricated via green wet-spinning process. The FT-IR and EDS determination indicated there formed egg-box between SA and Ca2+, cross-linked network between glutaraldehyde(GA) and SA, QAC, respectively. Depending on its mechanical, natural, and antibacterial properties, the SA/QAC composite fiber has advantages in wound dressing, medical gauze, medical absorbable suture, and tissue engineering.

Fluorescent N-functionalized carbon nanodots from carboxymethylcellulose for sensing of high-valence metal ions and cell imaging.

A convenient and sensitive reversible-fluorescence sensing platform for accurate monitoring of high-valence metal ions is still very challenging. As a green kind of fluorescent carbon nanomaterials, carbon dots (CDs) have captured considerable attention because of the stable fluorescence property and low cost. Herein, we fabricated a type of nitrogen-functionalized carbon dots (N-CDs) from CMC as a fluorescent reversible sensing platform for detecting various high-valence metal ions. N-CDs with a mean size of 2.3 nm were obtained and possessed 22.9% quantum yields (QY). A label-free fluorescent probe for detection of high-valence metal ions (Fe3+, Cr6+, Mn7+) was established via the fluorescence quenching response. Among them, the detection limit (LOD) toward Fe3+ ions reached 0.8 µM. We have explored the quenching mechanism of N-CDs to explain the valence state-related electron-transfer fluorescence quenching between high-valence metal ions and N-CDs. Moreover, the valence state-related fluorescence quenching phenomenon of N-CDs in aqueous solution could be effectively recovered by introducing a reducing agent (Ti3+). This "turn off-on" fluorescence recovery system of N-CDs could be applied in different applications covering the selective detection of environmental high-valence metal ions and cellular imaging.

Adaptation in the Dorsal Belt and Core Regions of the Auditory Cortex in the Awake Rat.

The rat auditory cortex is divided anatomically into several areas, but little is known about the functional differences in information processing among these areas. Three tonotopically organized core fields, namely, the primary (A1), anterior (AAF), and ventral (VAF) auditory fields, as well as one non-tonotopically organized belt field, the dorsal belt (DB), were identified based on their response properties. Compared to neurons in A1, AAF and VAF, units in the DB exhibited little or no response to pure tones but strong responses to white noise. The few DB neurons responded to pure tones with thresholds greater than 60 dB SPL, which was significantly higher than the thresholds of neurons in the core regions. In response to white noise, units in DB showed significantly longer latency and lower peak response, as well as longer response duration, than those in the core regions. Responses to repeated white noise were also examined. In contrast to neurons in A1, AAF and VAF, DB neurons could not follow repeated stimulation at a 300 ms inter-stimulus interval (ISI) and showed a significant steeper ISI tuning curve slope when the ISI was increased from 300 ms to 4.8 s. These results indicate that the DB processes auditory information on broader spectral and longer temporal scales than the core regions, reflecting a distinct role in the hierarchical cortical pathway.

Component Identification and Functional Analysis of Outer Membrane Vesicles Released by Avibacterium paragallinarum.

Avibacterium paragallinarum, the causative agent of infectious coryza, is known to release outer membrane vesicles (OMVs). In the present study, we investigated the composition, bioactivities, and functional properties of the OMVs of A. paragallinarum. Following extraction and purification, the OMVs were observed to be spherical in shape, with diameters ranging from 20 to 300 nm. The vesicles contained endotoxin as well as genomic DNA. The molecular weights of the OMV-contained protein fragments were mostly concentrated at 65 and 15 kDa. The components of the OMV proteins were mainly various functional enzymes (e.g., ATP-dependent RNA helicase), structural components (e.g., streptomycin B receptor and membrane protein), and some hypothetical proteins with unknown functions. The expression levels of inflammation-related factors, such as interleukin (IL)-2, IL-6, IL-1ß, IL-10, and inducible nitric oxide synthase (iNOs), were significantly upregulated in chicken macrophage cells HD11 incubated with OMVs. Serum IgG antibodies were measured after two intramuscular injections of an OMV-based vaccine into specific pathogen-free (SPF) chickens. The vaccinated chickens were then challenged by A. paragallinarum of homologous and heterologous serovars. It was noted that the vaccinated chickens produced immunoglobulin G (IgG) antibodies against A. paragallinarum. The OMVs conferred an acceptable level of protection (70%), defined as an absence of colonization and of clinical signs, against the homologous strain (serovar A), while the cross-protection against heterologous challenge with serovars B and C was much weaker. However, the OMVS did provide significant protection against clinical signs for all three serovars. Overall, this study laid a foundation for further unraveling the functional roles of OMVs released by A. paragallinarum.

Fe3O4@Carbon Nanofibers Synthesized from Cellulose Acetate and Application in Lithium-Ion Battery.

Fe3O4@CNF anode material for Li-ion batteries (LIBs) was designed and fabricated using lyotropic cellulose acetate as the carbon nanofiber (CNF) phase and Fe(acac)3 as the Fe3O4 phase through the electrospinning approach. Because the CNFs could retard the change of Fe3O4 volume during the electrochemical cycling and improve the electrical conductivity and the introduction of Fe3O4 could offer a larger specific surface area and more mesopores to promote electrolyte penetration and Li+ diffusion, the Fe3O4@CNFs electrode showed high reversible capacities (RCs) of 773.6 and 596.5 mAh g-1 after 300 cycles and capacity residuals of 98.0 and 99.0% at high current densities 1 and 2 A g-1, respectively. This simple method to fabricate Fe3O4@CNFs composite as anode material can be widely applied to fabricate metal oxides and bio-carbon composite nanofibers for high-performance energy storage materials.

Effect of Coagulation Bath Temperature on Mechanical, Morphological, and Thermal Properties of Cellulose/Antarctic Krill Protein Composite Fibers.

Cellulose (C) and Antarctic krill protein (AKP) were dissolved at low temperature, and then C/AKP composite fibers were prepared by wet spinning. In this paper, the effect of coagulation bath temperature on the properties of C/AKP composite fibers were studied by FT-IR, XRD, DSC, and other tests. The results showed that, when the temperature of the coagulation bath increased from 5 to 25 °C, the intermolecular hydrogen bond content of the C/AKP composite fibers increased from 28.20% to 31.33%. When the coagulation bath temperature is 15 °C, the breaking strength of the composite fibers is 1.64cN/dtex, which is 12% higher than that of the composite fibers at room temperature. At this temperature, the crystallinity of the composite fibers is improved, the thermal stability is slightly improved, and the surface morphology is smoother. Inspiringly, when zinc sulfate is added to the coagulation bath, the formation process of the fibers is milder. Moreover, the C/AKP composite fibers have excellent antibacterial activity against Escherichia coli and Staphylococcus aureus.

A sodium alginate/feather keratin composite fiber with skin-core structure as the carrier for sustained drug release.

To alleviate the serious gastrointestinal side reaction of indomethacin (IDM), sodium alginate/feather keratin (SA/FK) fiber with skin-core structure was prepared via wet spinning as the carrier for sustained release of IDM. Fourier translation infrared (FT-IR) spectroscopy was adopted to investigate the reaction mechanism among SA, FK and IDM, and Ultraviolet-visible (UV-Vis) spectroscopy was used to systematically evaluate the sustained release capacity of SA/FK fiber in three simulated fluids. Scanning electron microscope (SEM) was employed to observe the apparent morphology of SA/FK fiber. The results indicate that, release amount of IDM exhibits an increase trend along with time; the release amount of IDM reaches 80% after 12 h in colon fluid and small intestinal fluid, and is less than 20% in digestive fluid. Simultaneously, FK can effectively control the release of IDM, and with the increase of FK content, IDM release time of the carrier fiber extends.

Formaldehyde-Controlled Synthesis of Multishelled Hollow Mesoporous SiO2 Microspheres.

We developed a facile one-pot method to synthesize multishelled hollow mesoporous SiO2 microspheres (HMSs) with controllable interior structures including one-shell, double-shell, and yolk-shell. Single reagent formaldehyde could fully control the morphology of HMSs, in that formaldehyde was crucial to the SiO2 precursor's hydrolysis rate and the template pore size.

Integrative stimulus-specific adaptation of the natural sounds in the auditory cortex of the awake rat.

Using oddball stimulus with pure tones, researchers have extensively investigated stimulus-specific adaptation (SSA), which has been regarded as a method of novelty detection, from the inferior colliculus (IC) to the auditory cortex (AC). However, until now, it is not clear whether SSA is preserved for natural sounds or whether it exists for spatial cues in the AC. Moreover, it is also unclear whether SSA integrates different types of cues within a single modality such as sound location and sound identity. Here, we addressed these issues using two natural sounds presented at two different locations while simultaneously performing extracellular recordings in the AC of awake rats. Our data showed that SSA was present in the AC for the natural sounds, the pure tones, and the spatial locations in the neuronal population. We also found that the AC response to a double deviant stimulus (a deviant sound at a deviant location) was stronger than that to a single (either a deviant sound or the same sound at a deviant location); this finding suggests that detecting unexpected events benefits from the integration of different cues within the same modality.

Sodium alginate/feather keratin-g-allyloxy polyethylene glycol composite phase change fiber.

In this study, the novel sodium alginate/feather keratin-g-allyloxy polyethylene glycol (SA/FK-g-APEG) composite phase change fiber was designed and fabricated via centrifugal spinning for the first time. The chemical structure of the composite fiber was characterized by FT-IF and NMR, the thermal property was characterized by DSC, and the morphology features was analyzed by SEM and EDS. The NMR result demonstrates there are chemical shifts at δ = 155.6 ppm indicating CC has been successfully introduced via acylation，and at δ = 70.06 ppm indicating that allyloxy polyethylene glycol (APEG) has been grafted onto feather keratin (FK). The DSC results show an decline in the endothermic peak related to melting of the APEG from 54.87 °C to 40.1 °C (phase change fiber), indicating the strong interaction between sodium alginate (SA) and feather keratin-g-allyloxy polyethylene glycol (FK-g-APEG). The mechanical properties test shows that the optimal spinning temperature is 40 °C, and the optimal Centrifugal speed is 500 r/min.