Swallowing rehabilitation of patients undergoing T-tube implantation for the treatment of laryngotracheal stenosis.

OBJECTIVE: Patients with laryngotracheal stenosis (LTS) often have dysphagia after laryngotracheal reconstruction with T-tube insertion, which affects the quality of life. The purpose of this study is to observe the effect of swallowing rehabilitation therapy on the improvement of quality of life in patients of otolaryngology-head and neck surgery with dysphagia undergoing T-tube implantation treatment through longitudinal study. METHODS: Thirty-eight patients with LTS who experienced dysphagia after laryngotracheal reconstruction and T-tube implantation were recruited. All patients received swallowing rehabilitation therapy. The assessment of swallowing function was performed using the 10-item Eating Assessment Tool (EAT-10), the 30 mL water swallow test (WST), and flexible endoscopic evaluation of swallow (FEES). RESULTS: After swallowing rehabilitation therapy, timing of swallowing, grade of dysphagia, performance on FEES and 30 mL WST, and EAT-10 score all improved. Thirty-eight patients successfully transitioned to oral feeding and were able to remove their nasogastric tubes without experiencing any complications, including aspiration pneumonia. CONCLUSION: For patients with LTS who experienced dysphagia after laryngotracheal reconstruction and T-tube implantation, swallowing rehabilitation therapy could improve swallowing function of the patients, so as to reduce the potential harm caused by the pain and complications of surgery experienced by patients.

Label-free plasmonic spectral profiling of serum DNA.

Genetic and epigenetic modifications are linked to the activation of oncogenes and inactivation of tumor suppressor genes. Likewise, the associated molecular alternations can best inform precision medicine for personalized tumor treatment. Therefore, performing characterization of genetic and epigenetic alternations at the molecular level represents a crucial step in early diagnosis and/or therapeutics of cancer. However, the prevailing methods for DNA analysis involve a series of tedious and complicated steps, in which important genetic and epigenetic information could be lost or altered. To provide a potential approach for non-invasive, direct, and efficient DNA analysis, herein, we present a promising strategy for label-free molecular profiling of serum DNA in its pristine form by fusing surface-enhanced Raman spectroscopy with machine learning on a superior plasmonic nanostructured platform. Using DNA methylation and single-point mutation as two case studies, the presented strategy allows a well-balanced sensitive and specific detection of epigenetic and genetic changes at the single-nucleotide level in serum. We envision the presented label-free strategy could serve as a versatile tool for direct molecular profiling in pristine forms of a wide range of biological markers and aid biomedical diagnostics as well as therapeutics.

Silver-Coordinated Watson-Crick Pairing-Driven Three-Dimensional DNA Walker for Locus-Specific Detection of Genomic N6-Methyladenine and N4-Methylcytosine at the Single-Molecule Level.

N6-Methyladenine (6mdA) and N4-methylcytosine (4mdC) are the two most dominant DNA modifications in both prokaryotes and eukaryotes, but standard hybridization-based techniques cannot be applied for the 6mdA/4mdC assay. Herein, we demonstrate the silver-coordinated Watson-Crick pairing-driven three-dimensional (3D) DNA walker for locus-specific detection of genomic 6mdA/4mdC at the single-molecule level. 6mdA-DNA and 4mdC-DNA can selectively hybridize with the binding probes (BP1 and BP2) to form 6mdA-DNA-BP1 and 4mdC-DNA-BP2 duplexes. The 6mdA-C/4mdC-A mismatches cannot be stabilized by AgI, and thus, 18-nt BP1/BP2 cannot be extended by the catalysis of KF exonuclease. Through toehold-mediated strand displacement (TMSD), the signal probe (SP1/SP2) functionalized on the gold nanoparticles (AuNPs) can competitively bind to BP1/BP2 in 6mdA-DNA-BP1/4mdC-DNA-BP2 duplex to obtain SP1-18-nt BP1 and SP2-18-nt BP2 duplexes. The resulting DNA duplexes can act as the substrates of lambda exonuclease, leading to the cleavage of SP1/SP2 and the release of Cy3/Cy5 and 18-nt BP1/BP2. The released 18-nt BP1/BP2 can subsequently serve as the walker DNA, moving along the surface of the AuNP to activate dynamic 3D DNA walking and releasing abundant Cy3/Cy5. The released Cy3/Cy5 can be quantified by single-molecule imaging. This nanosensor exhibits high sensitivity with a limit of detection (LOD) of 9.80 × 10-15 M for 6mdA-DNA and 9.97 × 10-15 M for 4mdC-DNA. It can discriminate 6mdA-/4mdC-DNA from unmodified genomic DNAs, distinguish 0.01% 6mdA-/4mdC-DNA from excess unmethylated DNAs, and quantify 6mdA-/4mdC-DNA at specific sites in genomic DNAs of liver cancer cells and Escherichia coli plasmid cloning vector, providing a new platform for locus-specific analysis of 6mdA/4mdC in genomic DNAs.

Molecular Regulatory Mechanism of Exogenous Hydrogen Sulfide in Alleviating Low-Temperature Stress in Pepper Seedlings.

Pepper (Capsicum annuum L.) is sensitive to low temperatures, with low-temperature stress affecting its plant growth, yield, and quality. In this study, we analyzed the effects of exogenous hydrogen sulfide (H2S) on pepper seedlings subjected to low-temperature stress. Exogenous H2S increased the content of endogenous H2S and its synthetase activity, enhanced the antioxidant capacity of membrane lipids, and protected the integrity of the membrane system. Exogenous H2S also promoted the Calvin cycle to protect the integrity of photosynthetic organs; enhanced the photosynthetic rate (Pn), stomatal conductance (Gs), transpiration rate (Tr), and photosynthesis; and reduced the intercellular CO2 concentration (Ci). Moreover, the activities of superoxide dismutase, peroxidase, catalase, and anti-cyclic glutathione (ASA-GSH) oxidase were improved to decompose excess reactive oxygen species (ROS), enhance the oxidative stress and detoxification ability of pepper seedlings, and improve the resistance to low-temperature chilling injury in 'Long Yun2' pepper seedlings. In addition, the H2S scavenger hypotaurine (HT) aggravated the ROS imbalance by reducing the endogenous H2S content, partially eliminating the beneficial effects of H2S on the oxidative stress and antioxidant defense system, indicating that H2S can effectively alleviate the damage of low temperature on pepper seedlings. The results of transcriptome analysis showed that H2S could induce the MAPK-signaling pathway and plant hormone signal transduction; upregulate the expression of transcription factors WRKY22 and PTI6; induce defense genes; and activate the ethylene and gibberellin synthesis receptors ERF1, GDI2, and DELLA, enhancing the resistance to low-temperature chilling injury of pepper seedlings. The plant-pathogen interaction was also significantly enriched, suggesting that exogenous H2S also promotes the expression of genes related to plant-pathogen interaction. The results of this study provide novel insights into the molecular mechanisms and genetic modifications of H2S that mitigate the hypothermic response.

Foliar application of salicylic acid inhibits the cadmium uptake and accumulation in lettuce (Lactuca sativa L.).

Introduction: Salicylic acid (SA) is a multi-functional endogenous phytohormone implicated in the growth, development, and metabolism of many plant species. Methods: This study evaluated the effects of different concentrations of SA (0, 25, 100, 200, and 500 mg/L) on the growth and cadmium (Cd) content of lettuce (Lactuca sativa L.) under Cd stress. The different concentrations of SA treatments were administered through foliar application. Results: Our results showed that 100-200 mg/L SA significantly increased the plant height and biomass of lettuce under Cd stress. When SA concentration was 200 mg/L, the plant height and root length of lettuce increased by 19.42% and 22.77%, respectively, compared with Cd treatment alone. Moreover, 200 mg/L and 500mg/L SA concentrations could reduce peroxidase (POD) and superoxide dismutase (SOD) activities caused by Cd stress. When the concentration of exogenous SA was 500 mg/L, the POD and SOD activities of lettuce leaves decreased by 15.51% and 19.91%, respectively, compared with Cd treatment. A certain concentration of SA reduced the uptake of Cd by the lettuce root system and the transport of Cd from the lettuce root system to shoots by down-regulating the expression of Nramp5, HMA4, and SAMT, thus reducing the Cd content of lettuce shoots. When the concentration of SA was 100 mg/L, 200 mg/L, and 500 mg/L, the Cd contents of lettuce shoots were 11.28%, 22.70%, and 18.16%, respectively, lower than that of Cd treatment alone. Furthermore, principal component and correlation analyses showed that the Cd content of lettuce shoots was correlated with plant height, root length, biomass, antioxidant enzymes, and the expression level of genes related to Cd uptake. Discussion: In general, these results provide a reference for the mechanism by which SA reduces the Cd accumulation in vegetables and a theoretical basis for developing heavy metal blockers with SA components.

Intercropping affects the physiology and cadmium absorption of pakchoi, lettuce, and radish seedlings.

Intercropping can affect the growth and elemental absorption of vegetables. This study investigated the physiology and cadmium (Cd) content of pakchoi (Brassica chinensis L.), lettuce (Lactuca sativa L. var. ramosa Hort.), and radish (Raphanus sativus L.) seedlings under monoculture, mutual intercropping of two or three varieties. Intercropping is not conducive to the accumulation of chlorophyll and biomass content of pakchoi, lettuce, and radish. When three seedlings were intercropped together, the antioxidant enzyme activity of pakchoi, lettuce, and radish increased and the content of malondialdehyde decreased, except that the superoxide dismutase activity of radish is inferior to the value of radish and pakchoi intercropping. Intercropping increased the soluble sugar and proline content in the lettuce seedlings, while those in the radish and lettuce seedlings reduced or had no significant effect. When intercropped with pakchoi and lettuce, the Cd content in the roots and shoots of pakchoi is higher and lower, respectively. At the same time, root or shoot bio-concentration factors also performed the same trend, and TF was the smallest and less than 1; however, the TF of lettuce is greater than 1. When intercropping with pakchoi or lettuce separately or together, it promoted the accumulation of Cd in radish root; when intercropping with pakchoi, the value of TF was the smallest. From the antioxidant system, the performance of the three seedlings intercropped together is better than the two; however, the accumulation of Cd shows the opposite trend, and the participation of cabbage in the intercropping is relatively conducive to reducing the Cd content in the edible parts.

Comparative Analysis of Italian Lettuce (Lactuca sativa L. var. ramose) Transcriptome Profiles Reveals the Molecular Mechanism on Exogenous Melatonin Preventing Cadmium Toxicity.

Cadmium (Cd) accumulation in lettuce causes a large amount of yield loss during industry. Although many studies report that exogenous melatonin helps to alleviate the Cd stress of lettuce, the molecular mechanism for how plant tissue responds to Cd treatment is unclear. Herein, we applied both PacBio and Illumina techniques for Italian lettuce under different designed treatments of Cd and melatonin, aiming to reveal the potential molecular pathway of the response to Cd stress as well as the how the pre-application of exogenous melatonin affect this process. This result reveals that the root has the biggest expression pattern shift and is a more essential tissue to respond to both Cd and melatonin treatments than leaves. We reveal the molecular background of the Cd stress response in prospects of antioxidant and hormone signal transduction pathways, and we found that their functions are diverged and specifically expressed in tissues. We also found that candidate genes related to melatonin detoxify during Cd stress. Our study sheds new light for future research on how melatonin improves the cadmium resistance of lettuce and also provide valuable data for lettuce breeding.

cGAS exacerbates Schistosoma japonicum infection in a STING-type I IFN-dependent and independent manner.

Schistosomiasis, which is caused by infection with Schistosoma spp., is characterized by granuloma and fibrosis in response to egg deposition. Pattern recognition receptors are important to sense invading Schistosoma, triggering an innate immune response, and subsequently shaping adaptive immunity. Cyclic GMP-AMP synthase (cGAS) was identified as a major cytosolic DNA sensor, which catalyzes the formation of cyclic GMP-AMP (cGAMP), a critical second messenger for the activation of the adaptor protein stimulator of interferon genes (STING). The engagement of STING by cGAMP leads to the activation of TANK-binding kinase 1 (TBK1), interferon regulatory factor 3 (IRF3), and the subsequent type I interferon (IFN) response. cGAS is suggested to regulate infectious diseases, autoimmune diseases, and cancer. However, the function of cGAS in helminth infection is unclear. In this study, we found that Cgas deficiency enhanced the survival of mice infected with S. japonicum markedly, without affecting the egg load in the liver. Consistently, Cgas deletion alleviated liver pathological impairment, reduced egg granuloma formation, and decreased fibrosis severity. In contrast, Sting deletion reduced the formation of egg granulomas markedly, but not liver fibrosis. Notably, Cgas or Sting deficiency reduced the production of IFNß drastically in mice infected with S. japonicum. Intriguingly, intravenous administration of recombinant IFNß exacerbated liver damage and promoted egg granuloma formation, without affecting liver fibrosis. Clodronate liposome-mediated depletion of macrophages indicated that macrophages are the major type of cells contributing to the induction of the type I IFN response during schistosome infection. Moreover, cGAS is important for type I IFN production and phosphorylation of TBK1 and IRF3 in response to stimulation with S. japonicum egg- or adult worm-derived DNA in macrophages. Our results clarified the immunomodulatory effect of cGAS in the regulation of liver granuloma formation during S. japonicum infection, involving sensing schistosome-derived DNA and producing type I IFN. Additionally, we showed that cGAS regulates liver fibrosis in a STING-type I-IFN-independent manner.

A controlled T7 transcription-driven symmetric amplification cascade machinery for single-molecule detection of multiple repair glycosylases.

Genomic oxidation and alkylation are two of the most important forms of cytotoxic damage that may induce mutagenesis, carcinogenicity, and teratogenicity. Human 8-oxoguanine (hOGG1) and alkyladenine DNA glycosylases (hAAG) are responsible for two major forms of oxidative and alkylative damage repair, and their aberrant activities may cause repair deficiencies that are associated with a variety of human diseases, including cancers. Due to their complicated catalytic pathways and hydrolysis mechanisms, simultaneous and accurate detection of multiple repair glycosylases has remained a great challenge. Herein, by taking advantage of unique features of T7-based transcription and the intrinsic superiorities of single-molecule imaging techniques, we demonstrate for the first time the development of a controlled T7 transcription-driven symmetric amplification cascade machinery for single-molecule detection of hOGG1 and hAAG. The presence of hOGG1 and hAAG can remove damaged 8-oxoG and deoxyinosine, respectively, from the dumbbell substrate, resulting in breaking of the dumbbell substrate, unfolding of two loops, and exposure of two T7 promoters simultaneously. The T7 promoters can activate symmetric transcription amplifications with the unfolded loops as the templates, inducing efficient transcription to produce two different single-stranded RNA transcripts (i.e., reporter probes 1 and 2). Reporter probes 1 and 2 hybridize with signal probes 1 and 2, respectively, to initiate duplex-specific nuclease-directed cyclic digestion of the signal probes, liberating large amounts of Cy3 and Cy5 fluorescent molecules. The released Cy3 and Cy5 molecules can be simply measured by total internal reflection fluorescence-based single-molecule detection, with the Cy3 signal indicating the presence of hOGG1 and the Cy5 signal indicating the presence of hAAG. This method exhibits good specificity and high sensitivity with a detection limit of 3.52 × 10-8 U µL-1 for hOGG1 and 3.55 × 10-7 U µL-1 for hAAG, and it can even quantify repair glycosylases at the single-cell level. Moreover, it can be applied for the measurement of kinetic parameters, the screening of potential inhibitors, and the detection of repair glycosylases in human serum, providing a new paradigm for repair enzyme-related biomedical research, drug discovery, and clinical diagnosis.

IL-17A-producing γδ T cells promote liver pathology in acute murine schistosomiasis.

BACKGROUND: The main symptoms of schistosomiasis are granuloma and fibrosis, caused by Schistosoma eggs. Numerous types of cells and cytokines are involved in the progression of Schistosoma infection. As a class of innate immune cells, γδ T cells play critical roles in the early immune response. However, their role in modulating granuloma and fibrosis remains to be clarified. METHODS: Liver fibrosis in wild-type (WT) mice and T cell receptor (TCR) δ knockout (KO) mice infected with Schistosoma japonicum was examined via Masson's trichrome staining of collagen deposition and quantitative reverse transcriptase-PCR (RT-PCR) of fibrosis-related genes. Granuloma was detected by hematoxylin-eosin (H&E) staining and quantified. Flow cytometry was used for immune cell profiling and for detecting cytokine secretion. The abundance of the related cytokines was measured using quantitative RT-PCR. RESULTS: The livers of S. japonicum-infected mice had significantly increased proportions of interleukin (IL)-17A producing γδ T cells and secreted IL-17A. Compared with the WT mice, TCR δ deficiency resulted in reduced pathological impairment and fibrosis in the liver and increased survival in infected mice. In addition, the profibrogenic effects of γδ T cells in infected mice were associated with enhanced CD11b+Gr-1+ cells, concurrent with increased expression of transforming growth factor (TGF)-ß in the liver. CONCLUSIONS: In this mouse model of Schistosoma infection, γδ T cells may promote liver fibrosis by recruiting CD11b+Gr-1+ cells. These findings shed new light on the pathogenesis of liver pathology in murine schistosomiasis.

Decoding Live Cell Interactions with Multi-Nanoparticle Systems: Differential Implications for Uptake, Trafficking, and Gene Regulation.

Surface modification with oligonucleotides renders gold nanoparticles to endocytose through very different pathways as compared to unmodified ones. Such oligonucleotide-modified gold nanoparticles (OGNs) have been exploited as effective nanocarriers for gene regulation therapies. Notably, in an effort to reduce overall dosage and provide safer transition to the clinic, cooperative systems composed of two or more discrete nanomaterials have been recently proposed as an alternative to intrinsically multifunctional nanoparticles. Yet, our understanding of such systems designed to synergistically cooperate in their diagnostic or therapeutic functions remains acutely limited. Specifically, cellular interactions and uptake of OGNs are poorly understood when the cell simultaneously interacts with other types of nanoparticles. Here, we investigated the impact of simultaneous uptake of similar-sized iron oxide nanoparticles (IOPs) on the endocytosis and gene regulation function of OGNs, whose analogues have been proposed for sensitization, targeting, and treatment of tumors. We discovered that both the OGN uptake amount and, remarkably, the gene regulation function remained stable when exposed to a very wide range of extracellular concentrations of IOPs. Additionally, the co-localization analysis showed that a proportion of OGNs was co-localized with IOPs inside cells, which hints at the presence of similar trafficking pathways for OGNs and IOPs following endocytosis. Taken together, our observations indicate that while the OGN endocytosis is highly independent of the IOP endocytosis, it shares transport pathways inside cells-but does so without affecting the gene regulation behavior. These results provide key insights into concomitant interactions of cells with diverse nanoparticles and offer a basis for the future design and optimization of cooperative nanomaterials for diverse theranostic applications.

[Treatment for posterior root tear of lateral meniscus through bone tunnel suture under arthroscopy].

OBJECTIVE: To evaluate clinical effects of posterior root tear of lateral meniscus through bone tunnel suture under arthroscopy. METHODS: From January 2012 to December 2014, 23 patients with posterior root tear of lateral meniscus repaired through bone tunnel suture under arthroscopy, including 15 males and 8 females, aged from 19 to 48 years old with an average age of (25.0±4.7) years old; 10 knees on the left side and 13 knees on the right side. Complications were observed, Lysholm score before and after operation at 12 months were used to evaluate clinical results, and VAS score was applied to assess pain relief. MRI was used to check recovery outcomes of lateral meniscus injury. RESULTS: All patients were followed up from 13 to 24 months with an average of (17.0±4.3) months. No injury of vessels, nerve and incision infection occurred. Motion of knee joint of 19 patients reached normal, 4 patients manifested limited activity of knee joint at12 months after operation. Postoperative Lysholm score 88.52±6.48 at 12 months was higher than that of before operation 46.12±7.35; Postoperative VAS score 0.8±0.7 at 12 months was lower than that of before operation 4.3±1.6. CONCLUSIONS: Bone tunnel suture under arthroscopy for the treatment of posterior root tear of lateral meniscus could relieve pain, decrease postoperative complications and obtain good clinical efficacy.

Promotion of neuronal regeneration by using self-polymerized dendritic polypeptide scaffold for spinal cord tissue engineering.

Tissue engineering technology is applicable for study of nerve regeneration after spinal cord injury. Many natural and artificial scaffold are not applicable because of poor mechanical properties and cell compatibility. Polypeptides with fine three-dimensional structure and cell compatibility and are widely used in tissue engineering research. The purpose of this study was to verify the neuronal differentiation of neural stem cells by using self-polymerize dendritic polypeptide for spinal cord tissue engineering. Neural stem cells were isolated from cerebral cortex of neonatal SD rats.Conventional media was triggered the 1wt% nano peptide solution self polymerizated to formed a nano gel. The gel was tested by scanning electron microscope and transmission electron microscope. Neural stem cells were inoculated onto gel or on Polylysine-coated slides with fetal bovine serum or not. SD rats were randomized divided into four groups. neural stem cells and self-polymerized peptide were transplanted into spinal cord injury models. Then we test the Density of NF-positive axons in the spinal cord injury area at 8 weeks after surgery and MS score of the locomotive function of hind limbs among mice of four groups. Neural stem cells were showed anti Nestin (+), anti NSE (+), anti GFAP (+). The gel tested by scanning electron microscope was showed thick wall structure, another one tested by transmission electron microscope was showed self-polymerized dendritic nanofibers, which contains several spacings. The cells in serum group were differentiate into neurons, but non serum group were not. These results suggest that the self-assembling peptide nanofiber scaffold(SAPNS) were cytocompatible to neural stem cells which were differentiated into neurons. A large number of axonal regeneration and recovery of joint function of hind limb were appeared. The self-polymerized Peptide maybe used as practical tissue engineering materials as future.

Comparison of minimally invasive plate osteosynthesis and conventional plate osteosynthesis for humeral shaft fracture: A meta-analysis.

BACKGROUND: The objective of this meta-analysis was to compare the efficacy and safety of minimally invasive plate osteosynthesis (MIPO) and conventional plate osteosynthesis (CPO) for humeral shaft fracture. METHODS: Potential academic articles were identified from the Cochrane Library, Medline (1966-2016.3), PubMed (1966-2016.3), Embase (1980-2016.3), and ScienceDirect (1966-2016.3). Gray studies were identified from the references of the included literature. Randomized controlled trials (RCTs) and non-RCT involving MIPO and CPO for humeral shaft fracture were included. Two independent reviewers performed independent data abstraction. I statistic was used to assess heterogeneity. Fixed or random effects model was used for meta-analysis. RESULTS: Two RCTs and 3 non-RCTs met the inclusion criteria. There was a lower incidence of iatrogenic radial nerve palsy in patients with MIPO (P = 0.006). There was no statistically significant difference in in the risk of developing nonunion, delay union, malformation, screw loosening, infection, operation time, UCLA, and MEPS function score between the 2 groups. CONCLUSION: MIPO decreased incidence of iatrogenic radial nerve palsy and is an efficacy and safety technique for humeral shaft fracture. Due to the limited quality and data of the evidence currently available, more high-quality RCTs are required.

[Tuberous sclerosis complex with refractory epilepsy: a clinicopathologic study of 14 cases].

OBJECTIVE: To study the clinicopathologic features of tuberous sclerosis complex (TSC). METHODS: The clinicopathologic data of the patients diagnosed as TSC with refractory epilepsy and resection of epileptic focus were retrospectively analyzed. RESULTS: Fourteen cases were included, the mean age was (15.8±12.9) years, with a male predominance (male to female ratio=10:4). Frontal lobe was the most common (13/14) site of involvement. MRI showed multiple patchy long T1 and long T2 signals. CT images showed multiple subependymal high density calcified nodules in nine cases. Histology showed mild to severe disruption of the cortical lamination, cortical and subcortical tubers with giant cells and/or dysmorphic neurons. The giant cells showed strong immunoreactivity for vimentin and nestin, while the dysmorphic neurons partially expressed MAP2 and NF. Vimentin also stained strongly the "reactive" astrocytes. Thirteen cases had follow-up information: Engel class I in six cases, Engel class II in six cases, and Engel class III in one case. CONCLUSIONS: Diagnosis of TSC relies on combined pathologic, clinical and neuroradiological features. Immunohistochemical staining can be helpful. Resection of epileptic focus is an effective method to treat refractory epilepsy in TSC.

Biomechanical study of the funnel technique applied in thoracic pedicle screw replacement.

BACKGROUND: Funnel technique is a method used for the insertion of screw into thoracic pedicle. AIM: To evaluate the biomechanical characteristics of thoracic pedicle screw placement using the Funnel technique, trying to provide biomechanical basis for clinical application of this technology. METHODS: 14 functional spinal units (T6 to T10) were selected from thoracic spine specimens of 14 fresh adult cadavers, and randomly divided into two groups, including Funnel technique group (n = 7) and Magerl technique group (n = 7). The displacement-stiffness and pull-out strength in all kinds of position were tested and compared. RESULTS: Two fixed groups were significantly higher than that of the intact state (P < 0.05) in the spinal central axial direction, compression, anterior flexion, posterior bending, lateral bending, axial torsion, but there were no significant differences between two fixed groups (P > 0.05). The mean pull-out strength in Funnel technique group (789.09 ± 27.33) was lower than that in Magerl technique group (P < 0.05). CONCLUSIONS: The Funnel technique for the insertion point of posterior bone is a safe and accurate technique for pedicle screw placement. It exhibited no effects on the stiffness of spinal column, but decreased the pull-out strength of pedicle screw. Therefore, the funnel technique in the thoracic spine affords an alternative for the standard screw placement.

TLR3 regulates mycobacterial RNA-induced IL-10 production through the PI3K/AKT signaling pathway.

Cytokine induction in response to Mycobacterium tuberculosis (Mtb) infection is critical for pathogen control, by (i) mediating innate immune effector functions and (ii) instructing specific adaptive immunity. IL-10 is an important anti-inflammatory cytokine involved in pathogenesis of tuberculosis (TB). Here, we show that TLR3, a sensor of extracellular viral or host RNA with stable stem structures derived from infected or damaged cells, is essential for Mtb-induced IL-10 production. Upon Mycobacterium bovis Bacillus Calmette-Guérin (BCG) infection, TLR3(-/-) macrophages expressed lower IL-10 but higher IL-12p40 production, accompanied by reduced phosphorylation of AKT at Ser473. BCG-infected TLR3(-/-) mice exhibited reduced IL-10 but elevated IL-12 expression compared to controls. Moreover, higher numbers of splenic Th1 cells and reduced pulmonary bacterial burden and tissue damage were observed in BCG-infected TLR3(-/-) mice. Finally, BCG RNA induced IL-10 in macrophages via TLR3-mediated activation of PI3K/AKT. Our findings demonstrate a critical role of TLR3-mediated regulation in the pathogenesis of mycobacterial infection involving mycobacterial RNA, which induces IL-10 through the PI3K/AKT signaling pathway.

[Functional roles of macrophage migration inhibitory factor in anti-parasitic diseases].

Macrophage migration inhibitory factor (MIF) is an important proinflammatory and immunoregulatory mediator, which locates at the apex of the cascade of innate immune response. It also plays an important role in regulating adaptive immune responses and counter-regulating the immunosuppressive effect of glucocorticoid. MIF is actively involved in a series of cell processes such as cell proliferation and differentiation as well as cell apoptosis. MIF is reported to regulate the host immune response to parasitic infection. Interestingly, the ortholog of mammalian MIF was identified in multiple parasites such as Plasmodium spp., Leishmania major, Brugia malayi and so on, which is actively involved in the regulation of host-pathogen interaction and therefore provides a novel immune evasion mechanism. Therefore, development of small molecular inhibitors and vaccines against MIF will pave a new avenue for the prevention and treatment of related parasitic diseases.

Reconfigurable three-dimensional DNA nanostructures for the construction of intracellular logic sensors.

Right out of the (logic) gate: Logic gates made from 3D DNA nanotetrahedra were constructed that are responsive to various ions, small molecules, and short strands of DNA. By including dynamic sequences in one or more edges of the tetrahedra, a FRET signal can be generated in the manner of AND, OR, XOR, and INH logic gates, as well as a half-adder circuit. These DNA logic gates were also applied to intracellular detection of ATP.

Effect of graphene oxide on undifferentiated and retinoic acid-differentiated SH-SY5Y cells line.

Graphene oxide (GO), has created an unprecedented opportunity for development and application in biology, due to its abundant functional groups and well water solubility. Recently, the potential toxicity of GO in the environment and in humans has garnered more and more attention. In this paper, we systematically studied the cytotoxicity of GO nanosheets via examining the effect of GO on the morphology, viability and differentiation of a human neuroblastoma SH-SY5Y cell line, which was an ideal model used to study neuronal disease in vitro. The results suggested that GO had no obvious cytotoxicity at low concentration (<80 µg mL(-1)) for 96 h, but the viability of cells exhibited dose- and time-dependent decreases at high concentration (≥ 80 µg mL(-1)). Moreover, GO did not induce apoptosis. Very interestingly, GO significantly enhanced the differentiation of SH-SY5Y induced-retinoic acid (RA) by evaluating neurite length and the expression of neuronal marker MAP2. These data provide a promising application for neurodegenerative diseases.