Polyphenol-Inspired Facile Construction of Smart Assemblies for ATP- and pH-Responsive Tumor MR/Optical Imaging and Photothermal Therapy.

Smart assemblies have attracted increased interest in various areas, especially in developing novel stimuli-responsive theranostics. Herein, commercially available, natural tannic acid (TA) and iron oxide nanoparticles (Fe3 O4 NPs) are utilized as models to construct smart magnetic assemblies based on polyphenol-inspired NPs-phenolic self-assembly between NPs and TA. Interestingly, the magnetic assemblies can be specially disassembled by adenosine triphosphate, which shows a stronger affinity to Fe3 O4 NPs than that of TA and partly replaces the surface coordinated TA. The disassembly can further be facilitated by the acidic environment hence causing the remarkable change of the transverse relaxivity and potent "turn-on" of fluorescence (FL) signals. Therefore, the assemblies for specific and sensitive tumor magnetic resonance and FL dual-modal imaging and photothermal therapy after intravenous injection of the assemblies are successfully employed. This work not only provides understandings on the self-assembly between NPs and polyphenols, but also will open new insights for facilely constructing versatile assemblies and extending their biomedical applications.

Plant Polyphenol-Assisted Green Synthesis of Hollow CoPt Alloy Nanoparticles for Dual-Modality Imaging Guided Photothermal Therapy.

Theranostic nanomedicines that integrate diagnostic and therapeutic moieties into a single nanoscale platform are playing an increasingly important role in fighting cancer. Here, a facile and green synthetic strategy for hollow CoPt alloy nanoparticles (HCPA-NPs) using plant polyphenols as assisted agents is reported for the first time. This novel strategy enables size-controlled synthesis of HCPA-NPs through the control of the molecular sizes of polyphenols. It is also a versatile strategy for synthesizing other hollow alloy nanoparticles with various metal compositions due to the diverse metal-chelating ability of the polyphenols. Further studies show that HCPA-NPs have good biocompatibility and can be successfully implemented for magnetic resonance and photoacoustic dual-modal imaging guided photothermal therapy. This work brings new insights for the green synthesis of hollow nanoparticles and extends these biocompatible nanoparticles for theranostic applications.

Functionalization of metal nanoclusters for biomedical applications.

Metal nanoclusters (NCs) are emerging as a new class of functional nanomaterials in the area of biological sensing, labelling, imaging and therapy due to their unique physical and chemical properties, such as ultrasmall size, HOMO-LUMO transition, strong luminescence together with good photostability and biocompatibility. A recent surge of interest in this field is the surface functionalization of these metal NCs through which one can tailor their physicochemical properties, such as stability in solution, and strong luminescence, as well as their biodistribution and toxicity in biological systems, which in turn can empower these functionalized NCs with desirable targeting, imaging, and therapeutic ability for biomedical applications. In this review, we first introduce the functionalization strategies for the metal NCs developed in the past few years, followed by highlighting some biomedical applications of these functionalized metal NCs. We then discuss the difference of in vitro and in vivo fate as well as toxicity between various functionalized metal NCs. Finally, we present a short discussion on the current challenges and provide an outlook of the future developments of these functional metal NCs.

Preventive effect of pidotimod on reactivated toxoplasmosis in mice.

As one of food-borne parasitic diseases, toxoplasmosis entails the risk of developing reactivation in immunocompromised patients. The synthetic dipeptide pidotimod is a potent immunostimulating agent that improves the immunodefenses in immunodepression. To investigate the efficacy of pidotimod as a preventive treatment, we used a murine model of reactivated toxoplasmosis with cyclophosphamide (CY)-induced immunosuppression. Pidotimod administration significantly restored the body weight and spleen organ index, increased survival time (from 70 to 90%), and decreased the parasitemia (from 80 to 35%) of CY-induced mice with reactivated toxoplasmosis. Cytokine profiles and CD4(+) T cells subpopulation analyses by Cytometric Bead Array and flow cytometry demonstrated that pidotimod treatment resulted in a significant upregulation of pro-inflammatory cytokines (IFN-γ, TNF-α, and IL-2) and Th1 cells (from 3.73 ± 0.39 to 5.88 ± 0.46%) after CY induction in infected mice. Additionally, histological findings and parasite DNA quantification revealed that mice administered with pidotimod had a remarkable reduction of parasite burden (two-log) and amelioration of histopathology in the brains. The in vitro studies showed that pidotimod significantly restored concanavalin A-induced splenocyte proliferation and pro-inflammatory cytokines in the supernatants of splenocyte culture. It could be concluded that the administration of pidotimod in immunocompromised mice significantly increases the Th1-biased immune response, prolongs survival time, and ameliorates the load of parasites in the blood. This is the first report of the preventive effect of pidotimod on reactivated toxoplasmosis.

[Kinetic distribution of cyst-forming Chinese isolate of Toxoplasma gondii in mice].

OBJECTIVE: To determine the kinetics of infection and cyst formation in CD1 mice following oral infection with cyst-forming Chinese isolate of Toxoplasma gondii TgCtwh1(genotype China 1, ToxoDB#9). METHODS: 50 CD1 female mice were obtained from specific pathogen-free (SPF) mouse colony in the Vital River Laboratories (VRL), Beijing. Mice were randomly divided into 10 groups each with 5 mice. All mice but control were peroral gavage infected with 50 cysts (1x10(4) bradyzoites) of TgCtwh1 isolate of T. gondii isolated from Wuhan, China. Cysts were isolated from the entire brain of mice infected with TgCtwh1 by density gradient centrifugation over Fycoll-paque plus. Animals were orally inoculated with cysts on day zero, and peripheral blood, lymph nodes, heart, liver, and brain of infected mice were collected on days 2, 4, 7, 10, 14, 21, 35, 50, and 72 post infection. Five mice were sacrificed by cervical dislocation under anesthesia at each time of collection, and the kinetic distribution was detected by fluorescence quantitative PCR and tissue inoculation into fresh mice. The cyst formation at various intervals after infection was also observed, as was the number of the cysts in brains and the cyst-forming rate. RESULTS: The body weight of the mice lessened (3.650 +/- 0.252)g post oral infection on day 7, and the weight was progressively decreased between day 10 [(1.730 +/- 0.017)g] and day 14 [(-0.390 +/- 0.554) g] after infection (P<0.05). In the brain tissue, cysts were first observed on day 21 post oral infection and the cyst-forming rate was 80%, and the average diameter of cysts was 20-40 microm. While on day 35 after infection, the cysts were formed in all infected mice(cyst-forming rate was 100%) and the average diameter was 50-60 microm. In chronic infection, DNA copies of parasites were first detected in blood, heart, liver and lymph node at 3.51 +/- 0.152, 4.100 +/- 0.198, 4.220 +/- 0.209 and 4.960 +/- 0.052 respectively on day 2, then in the brain on day 4 (3.800 +/- 0.154). During the early days of infection, the parasite burden in blood was progressively increased until days 7 (5.240 +/- 0.115) then gradually decreased and become undetectable on day 35. The burden of T. gondii in the heart and brain tissues increased significantly and reached their maximum on day 14 (5.640 +/- 0.214) and day 10 (5.790 +/- 0.060), respectively, and remained a stable level thereafter. Liver and lymph tissues reached their maximum on day 7 (5.310 +/- 0.038) and day 10 (6.200 +/- 0.152), then gradually decreased and become undetectable on day 50. CONCLUSION: The parasitemia in mice infected with T. gondii cyst-forming isolate lasts for 21 d at least, and cysts are detected in brain on day 21.

Evaluation of recombinant SjLAP and SjFBPA in detecting antibodies to Schistosoma japonicum.

OBJECTIVE: To investigate the early response of immunoglobulin G (IgG) antibody responses to Schistosoma japonicum infection in mice by using the recombinant proteins, S. japonicum leucine aminopeptidase (rSjLAP) and S. japonicum fructose-1, 6-bisphosphate aldolase (rSjFBPA), and evaluate the potential of rSjLAP and rSjFBPA in diagnosis as well as in assessment of therapeutic efficacy in human schistosomiasis. METHODS: rSjLAP or rSjFBPA was induced from Escherichia coli BL21 strain transfected with the expression vectors, pET-28a-rSjFBPA/BL21 or pET-28a-rSjLAP/BL21 using isopropyl-beta-D-thiogalactoside (IPTG), and purified by Ni-NTA His Bind resin. 88 BALB/c female mice, inbred and 6 to 8 weeks old, were randomly divided into 4 groups. Groups A, B and C each made up of 21 mice and group D comprised 25 mice. Groups A, B and C were infected with 5, 15 and 25 S. japonicum cercariae respectively. As control, mice in group D were left uninfected. 3 mice from each of groups A, B and C were sacrificed and sera collected on days 3, 7, 10, 14, 20, 30, and 60 post infection. All the 25 mice in group D were sacrificed on the first day of the experiment for serum collection. rSjLAP and rSjFBPA were screened and used in ELISA to test the antibody response of the serum samples. Also, sera of 38 acute patients, 96 chronic patients with schistosomiasis japonica, 90 healthy donors and patients with other parasite infections including Clonorchis sinensis (33 cases), Paragonimus westermani (40) and hookworms (37) were tested using the recombinant protein-based ELISA. In addition, 36 sera each from the acute and chronic patients 12 months after treatment with praziquantel and 64 of the chronic patients in more than 2 years post-treatment of praziquantel were tested. The dosage of praziquantel for both acute and chronic patients was 60 mg/kg, 2 times/dx2 d. RESULTS: IgG antibody response was first detected at day 10 post infection by rSjLAP, rSjFBPA or the combined antigen assay. The mean absorbance (A450) on this day were 0.535 +/- 0.053, 0.595 +/- 0.033, 0.696 +/- 0.104 for group B; 0.548 +/- 0.060, 0.608 +/- 0.063, 0.621 +/- 0.090 for group C; and 0.415 +/- 0.038, 0.455 +/- 0.056, 0.498 +/- 0.077 for group A for rSjLAP, rSjFBPA and the combined assay respectively (P < 0.05). Early antibody level to both antigens was significantly higher in mice infected with 15 or 25 cercariae than those with 5 cercariae (P < 0.05). However, ELISA results in patients with confirmed schistosomiasis revealed positive rates of 97.4% (37/38) and 87.5% (84/96) for acute and chronic schistosomiasis with rSjLAP , 94.7% (36/38) and 88.5% (85/96) for acute and chronic schistosomiasis with rSjFBPA and 94.7% (36/38)and 85.4%(82/96) with both rSjLAP and rSjFBPA respectively. Statistical analysis showed no significant difference in the positive rate (P > 0.05). Also, rSjLAP and combined antigens showed a specificity of 96.7% (87/90) while that of rSjFBPA was 97.8% (88/90). There was a general decrease in the antibody titer of the patients after treatment. In 12 months after treatment it was 0.236 +/- 0.212 with rSjLAP, 0.287 +/- 0.191 with rSjFBPA, and 0.235 +/- 0.120 with both antigens respectively for acute cases; For chronic patients, it was 0.266 +/- 0.124, 0.261 +/- 0.143 and 0.265 +/- 0.140 in 12 months post-treatment, and 0.204 +/- 0.074, 0.176 +/- 0.074, and 0.176 +/- 0.073 in 2 years, respectively. For healthy control, it was 0.188 +/- 0.056, 0.173 +/- 0.45, and 0.184 +/- 0.051, respectively. No significant difference on antibody titer was found between treated patients and control (P > 0.05). The cross reaction with C. sinensis was 15.2% (5/33) for rSjLAP, 12.1% (4/33) for rSjFBPA and 9.2% (3/33) for combined antigens. With P. westermani, it was 15.0% (6/40), 12.5% (5/40) and 15.0% (6/40), respectively, and 8.1% (3/37) with hookworm infection. CONCLUSION: The study showed a satisfactory sensitivity and specificity of rSjLAP and rSjFBPA by ELISA which is promising for the immunological diagnosis of schistosomiasis.

The Sensory Abnormality Mediated Partially the Efficacy of Repetitive Transcranial Magnetic Stimulation on Treating Comorbid Sleep Disorder in Autism Spectrum Disorder Children.

Sleep disorder emerges as a common comorbidity in children with autism spectrum disorder (ASD), and the interaction between the core symptoms of ASD and its sleep disorder remains unclear. Repetitive transcranial magnetic stimulation (rTMS) was used on the bilateral dorsolateral prefrontal cortex (DLPFC) to investigate the efficacy of rTMS on the core symptoms of ASD and comorbid sleep problems as well as the mediation role of the ASD symptoms between rTMS intervention and sleep improvement. A total of 41 Chinese children with ASD and who met the criteria in the fifth edition of the American Diagnostic and Statistical Manual of Mental Disorders were recruited, and 39 of them (mean age: 9.0 ± 4.4 years old; the male-female ratio was 3.9: 1) completed the study with the stimulating protocol of high frequency on the left DLPFC and low frequency on the right DLPFC. They were all assessed three times (before, at 4 weeks after, and at 8 weeks after the stimulation) by the Children's Sleep Habits Questionnaire (CSHQ), Strengths and Difficulties Questionnaire (SDQ), Childhood Autism Rating Scale, Repetitive Behavior Questionnaire-2, and Short Sensory Profile (SSP). The repeated-measures ANOVA showed that the main effect of "intervention time" of CSHQ (F = 25.103, P < 0.001), SSP (F = 6.345, P = 0.003), and SDQ (F = 9.975, P < 0.001) was statistically significant. By Bayesian mediation analysis, we only found that the total score of SSP mediated the treating efficacy of rTMS on CSHQ (αß = 5.11 ± 1.51, 95% CI: 2.50-8.41). The percentage of mediation effect in total effect was 37.94%. Our results indicated the treating efficacy of rTMS modulation on bilateral DLPFC for both autistic symptoms and sleep disturbances. The sensory abnormality of ASD mediated the improvement of rTMS on sleep problems of ASD.

Three-Dimensional Printing-Assisted Fabrication of Stent Graft to Reconstruct the Total Aortic Arch.

PURPOSE: There is a high incidence of complications after conventional open thoracic aortic arch replacement. Stent graft thoracic endovascular repair for aortic aneurysms has few complications. Vascular variability of the aortic arch branch is high and individualized aortic arch stent graft is required. We present our experience using 3-dimensional print-assisted fabrication of individualized stent grafts. DESCRIPTION: According to the patient's computed tomography angiography results before surgery, the aortic arch was printed 3-dimensionally and then an individualized stent graft was sewn. The prepared stents were placed in the descending aorta and the partial branches of the arch, and then released. EVALUATION: Intraoperative stent placement was successful. The deep hypothermic circulatory arrest time was only 5 minutes. The patient recovered well after surgery and no neurological complications occurred. Postoperative computed tomography angiography showed good stent expansion and no endoleak. CONCLUSIONS: Three-dimensional printing-assisted fabrication of a stent graft can be used for endovascular repair of the total aortic arch. This technology can be employed to construct individualized aortic arch stents accurately for different patients before surgery.

Sleep Problems Influence Emotional/Behavioral Symptoms and Repetitive Behavior in Preschool-Aged Children With Autism Spectrum Disorder in the Unique Social Context of China.

Sleep disturbances are common in people with autism spectrum disorder (ASD), but research on this topic is still limited in China. In the current study, we evaluated the prevalence of sleep problems in preschool-aged children with ASD and to examine the correlations between sleep disturbances and emotional/behavioral symptoms and repetitive behavior in the unique social context of China. This study recruited 475 preschool-aged children aged 3-6 years old, including 252 children with ASD (mean age 5.13 ± 1.15, 80.6% male) and 223 age-matched typically developing (TD) children (mean age 5.12 ± 0.97, 74.9% male). The parents of all children completed a sociodemographic questionnaire and the Childhood Sleep Habits Questionnaire. The parents of 114 ASD children completed the Strengths and Difficulties Questionnaire (SDQ) and the Repetitive Behavioral Questionnaire-2 (RBQ-2). The prevalence of sleep problems in preschool-aged children with ASD in this study was 81.7%, which was higher than that in TD children (61.0%). The scores for bedtime resistance, sleep anxiety, sleep duration, parasomnias, and sleep onset delay in the ASD group were significantly higher than those in the TD group (t=-7.664, P=0.000; t=-10.477, P=0.000; t=-4.133, P=0.000; Z=-3.916, P=0.000; Z=-7.093, P=0.000; respectively). Sleep onset delay explained 17.3% of the variance (adjusted R2 = 0.173) in the total SDQ score of children with ASD, and bedtime resistance explained a large proportion of total RBQ-2 score variance (adjusted R2 = 0.206). The high rate of sleep disturbances in preschool-aged children with ASD emphasizes the importance of screening for sleep problems in this population. Attention should also be directed toward formulating good sleep hygiene practices for preschool-aged children in the particular social context and cultural setting of China.

Hybrid procedure for treating adult congenital heart disease with valvular heart disease in two patients.

BACKGROUND: The traditional approach for adult congenital heart disease combined with valvular disease is surgical treatment under cardiopulmonary bypass (CPB). This approach has a high incidence of postoperative complications, especially in patients with pulmonary hypertension and old age. We present two patients in whom the hybrid procedure was used to treat congenital malformations, followed by valve formation and replacement surgery. CASE PRESENTATION: A 63-year-old man had a muscular ventricular septal defect complicated by mitral regurgitation and a 57-year-old man had patent ductus arteriosus complicated by aortic stenosis. In both of the patients, the congenital malformation was successfully treated by the hybrid procedure, followed by valve repair or replacement. Both patients had no complications. A post-procedure echocardiogram showed no residual shunt across the duct. CONCLUSIONS: Our findings suggest that the hybrid procedure is a useful alternative for treating adult congenital heart disease with valvular heart disease. This procedure reduces the surgical incision and difficulty of surgery, shortens the CPB time, avoids residual leakage after surgery, and reduces recovery and hospitalization times.

Enhancing Antitumor Efficacy by Simultaneous ATP-Responsive Chemodrug Release and Cancer Cell Sensitization Based on a Smart Nanoagent.

The exploitation of smart nanoagents based drug delivery systems (DDSs) has proven to be a promising strategy for fighting cancers. Hitherto, such nanoagents still face challenges associated with their complicated synthesis, insufficient drug release in tumors, and low cancer cell chemosensitivity. Here, the engineering of an adenosine triphosphate (ATP)-activatable nanoagent is demonstrated based on self-assembled quantum dots-phenolic nanoclusters to circumvent such challenges. The smart nanoagent constructed through a one-step assembly not only has high drug loading and low cytotoxicity to normal cells, but also enables ATP-activated disassembly and controlled drug delivery in cancer cells. Particularly, the nanoagent can induce cell ATP depletion and increase cell chemosensitivity for significantly enhanced cancer chemotherapy. Systematic in vitro and in vivo studies further reveal the capabilities of the nanoagent for intracellular ATP imaging, high tumor accumulation, and eventual body clearance. As a result, the presented multifunctional smart nanoagent shows enhanced antitumor efficacy by simultaneous ATP-responsive chemodrug release and cancer cell sensitization. These findings offer new insights toward the design of smart nanoagents for improved cancer therapeutics.

Repeatable deep-tissue activation of persistent luminescent nanoparticles by soft X-ray for high sensitivity long-term in vivo bioimaging.

Persistent luminescent nanoparticles (PLNPs) have emerged as important nanomaterials for biological imaging as a result of complete avoidance of tissue auto-fluorescence. However, the imaging sensitivity and long-term in vivo imaging are still limited due to the persistent luminescence that is rapidly decayed in vivo after an ex vivo excitation. To address this limitation, in vivo activation of PLNPs is highly desired. Herein, we present a new strategy for the activation of PLNPs (SrAl2O4:Eu2+) by using soft X-ray excitation. Importantly, as the soft X-ray light source possesses the advantage of deep tissue penetration, the PLNPs can be reactivated in vivo through living tissue using soft X-ray excitation. Furthermore, X-ray/persistent luminescence dual-modal imaging can be achieved to empower this strategy with high sensitivity. Our results suggest that this new strategy of in vivo energy charging in PLNPs would bring new insights for deep tissue and long-term bioimaging in living animals, and provide new perspectives for persistent luminescence bioimaging and therapeutic applications.

Co9 Se8 nanoplates as a new theranostic platform for photoacoustic/magnetic resonance dual-modal-imaging-guided chemo-photothermal combination therapy.

A new theranostic platform is developed based on biocompatible poly(acrylic acid) (PAA)-Co9 Se8 nanoplates. These PAA-Co9 Se8 nanoplates are successfully utilized for photoacoustic imaging (PAI)/magnetic resonance imaging (MRI) dual-modal imaging. Moreover, the PAA-Co9 Se8 -DOX shows pH-responsive chemotherapy and enables the combination of photothermal therapy and chemotherapy to receive superior antitumor efficacy. This work promises further exploration of 2D nanoplatforms for theranostic applications.

Topological insulator bismuth selenide as a theranostic platform for simultaneous cancer imaging and therapy.

Employing theranostic nanoparticles, which combine both therapeutic and diagnostic capabilities in one dose, has promise to propel the biomedical field toward personalized medicine. Here we investigate the theranostic properties of topological insulator bismuth selenide (Bi2Se3) in in vivo and in vitro system for the first time. We show that Bi2Se3 nanoplates can absorb near-infrared (NIR) laser light and effectively convert laser energy into heat. Such photothermal conversion property may be due to the unique physical properties of topological insulators. Furthermore, localized and irreversible photothermal ablation of tumors in the mouse model is successfully achieved by using Bi2Se3 nanoplates and NIR laser irradiation. In addition, we also demonstrate that Bi2Se3 nanoplates exhibit strong X-ray attenuation and can be utilized for enhanced X-ray computed tomography imaging of tumor tissue in vivo. This study highlights Bi2Se3 nanoplates could serve as a promising platform for cancer diagnosis and therapy.

Nicking enzyme based homogeneous aptasensors for amplification detection of protein.

A simple and highly sensitive homogeneous aptasensor is developed, which relies on nicking enzyme. The sensitivity of this newly proposed aptasensor is about three orders of magnitude higher than that of traditional homogeneous aptasensors. Furthermore, it is capable of detecting target protein in real samples.

A graphene oxide (GO)-based molecular beacon for DNA-binding transcription factor detection.

A GO-based molecular beacon assay was developed for rapid, sensitive and cost-efficient detection of transcription factor proteins. Furthermore, this assay can be employed for screening inhibitors of transcription factor proteins.

Enzyme-free fluorescence aptasensor for amplification detection of human thrombin via target-catalyzed hairpin assembly.

Aptamers have many advantages, such as simple synthesis, good stability, high binding affinity and wide applicability, making them suitable candidates for protein detection. Since the disease-related protein may be present in very small amounts in biological samples, the development of amplification paths for aptasensors is essential. In this paper, we develop a simple and enzyme-free amplified aptasensor for protein detection via target-catalyzed hairpin assembly. This aptasensor contains two DNA hairpins termed as H1 and H2. H1, which is modified at its 5' and 3' ends with a fluorophore and a quencher respectively, consists of the aptamer sequence of human thrombin. Meanwhile, H2 is partially complementary to H1. These two hairpins H1 and H2 interact slowly with each other. Upon the addition of target protein, it can facilitate the opening of the hairpin structure of H1 and thus accelerate the hybridization between H1 and H2, resulting in the significant fluorescence enhancement of the system. By monitoring the change in fluorescence intensity, we could detect the target protein with high sensitivity. The detection limit of this aptasensor is 20 pM, which is more than two orders of magnitude lower than that of reported unamplified aptasensors. Furthermore, this amplified aptasensor shows high selectivity toward its target protein. Thus, the proposed aptasensor could be used as a simple, sensitive and selective platform for target protein detection.

Label-free and fluorescence turn-on aptasensor for protein detection via target-induced silver nanoclusters formation.

A simple turn-on and homogeneous aptasensor, which relies on target induced formation of silver nanoclusters (Ag NCs), was developed for the determination of platelet-derived growth factor B-chain homodimer (PDGF-BB). The aptasensor contains two hairpin DNA probes termed as P1 and P2. P1 consists of the aptamer sequence of PDGF-BB. Meanwhile, P2 contains the Ag NCs nucleation sequence, which is blocked by the hairpin stem region. P1 and P2 can co-exist metastably in the absence of PDGF-BB and maintain hairpin structure. However, in the presence of PDGF-BB, the binding of PDGF-BB with aptamer will result in the hybridization between P1 and P2, and release the Ag NCs nucleation sequence. In this case, Ag NCs can be formed via the reduction of Ag(+) by NaBH(4). By monitoring the increase in fluorescence intensity, we could detect the target protein with high sensitivity. The detection limit of this aptasensor is 0.37 nM, which is comparable with that of other reported aptasensors. Furthermore, this proposed aptasensor shows high selectivity toward its target protein. Thus, the proposed aptasensor based on target induced formation of Ag NCs could be used as a sensitive and selective platform for the detection of target protein.

Enzyme-free signal amplification in the DNAzyme sensor via target-catalyzed hairpin assembly.

A simple, highly sensitive and enzyme-free DNAzyme sensor based on target-catalyzed hairpin assembly is developed, which permits detection of 0.1 pM target DNA. Furthermore, this DNAzyme sensor is capable of detecting target DNA in real samples because of its high selectivity.

Tim-2 up-regulation and galectin-9-Tim-3 pathway activation in Th2-biased response in Schistosoma japonicum infection in mice.

T cell immunoglobulin domain and mucin domain (Tim) family, a new gene that expresses on the surface of T cells, plays a critical role in regulation of T cells response. Previous data have shown that Tim-3 expressed on Th1 cells promotes itself apoptosis. Tim-2 is preferentially up-regulated during Th2 differentiation and functions as a potent costimulatory molecule for T-cell immunity. The present study aims to learn whether Tims are responsible for Th2-biased response evoked by Schistosoma japonicum infection. The expressions of Tim-2 and Tim-3 in spleen lymphocytes from S. japonicum-infected mice were examined, and the possible role of galectin-9-Tim-3 pathway in Th2-biased response triggered by schistosome infection was discussed. Our results showed that Tim-2 mRNAs were up-regulated in the spleen of schistosome-infected mice, which coincided with elevated IL-4 gene expression. Administration of galectin-9 significantly induced apoptosis of naïve spleen lymphocytes with down-regulation IFN-γexpression in vitro. Additionally, Tim-3-Fc fusion protein notably enhanced Th1 cells and decreased Th2 cells in vitro. Thus, we concluded that pro-apoptotic effects on Th1 population through galectin-9-Tim-3 pathway and the up-regulation of Tim-2 on Th2 cells might be critical to Th2-biased response of host with schistosomiasis japonica.