One-step preparation of nano-in-micro poly(vinyl alcohol) embolic microspheres and used for dual-modal T1/T2-weighted magnetic resonance imaging.

It is crucial to develop dual or multi-modal self-imaging embolic microspheres to evaluate the effects of transcatheter arterial embolization therapy of tumor. However, the preparation of such hybrid microspheres always involved in multiple steps or complicated conditions. Here, poly(vinyl alcohol) (PVA) hybrid microspheres with dual-modal T1/T2-weighted magnetic resonance imaging (MRI) have been prepared based on microfluidic technique in one step. Gd2O3 and Fe3O4 nanoparticles with a size of ~5 nm act as T1- and T2-weighted MRI contrast agents, respectively, which are simultaneously in-situ synthesized in the PVA matrix via the reaction of metal ions and alkali with PVA chains as a soft template. Meanwhile, these metallic-oxide nanoparticles act as cross-linker to gelatinize the PVA droplets to obtain nano-in-micro PVA microspheres in one step. This procedure is simple, economic and feasible. The obtained nano-in-micro PVA microspheres show good magnetothermal effect, enhanced T1- and T2-weighted MRI and embolization effect.

Microwave-assisted polyol synthesis of gadolinium-doped green luminescent carbon dots as a bimodal nanoprobe.

The development of multimodal nanoprobes is highly desired in medical imaging because it integrates the advantages of multiple imaging modes. In this study, the gadolinium-doped green luminescent carbon dots (Gd-CDs) were prepared by the simple one-step microwave-assisted polyol method. The obtained Gd-CDs emitted a unique green photoluminescence with a quantum yield of 5.4%. The Gd-CDs exhibited a low cytotoxicity and could optically label the C6 glioma cells. Meanwhile, the r1 relaxivity of Gd-CDs was measured to be 11.356 mM(-1) s(-1). This high r1 value together with the r2/r1 ratio close to 1 nominates Gd-CDs as an excellent T1 contrast agent for magnetic resonance imaging. These Gd-CDs combining two complementary imaging modalities are therefore a promising bimodal nanoprobe in medical imaging for a better diagnosis.

[Analysis on the impact of composting with different proportions of corn stalks and pig manure on humic acid fractions and IR spectral feature].

Using pig manure and corn straw as raw materials for high-temperature composting, setting three different treat- ments: C/N 15, C/N 25, and C/N 35. Composting period is 120 days, which contains 30 days for ventilation cycle by forced continuous ventilation. Sampled on 0, 22, 30, 60, 90, 120th days, they were analyzed by elemental analysis and IR spectroscopy to study effect of different lignin content on compost humic acid (HA) composition and molecular structure. The results showed that the change in composting humic acid C focused on the first 30 days, while after composting, the O/C of compost HA increased, H/C decreased, and N content increased. Low C/N (15) and higher C/N ratio (35) had higher degree of oxidation than the C/N 25 in compost HA. FTIR indicated that the infrared spectrum shapes with different lignin content treatment are similar during the composting process, but the peak intensity is obviously different. Research results proved that the composting stage is more conducive to enhanced aromatic in compost HA. After composting, C/N 15 had less polysaccharide and fat ingredients and more aromatic structural components in compost HA, compared with C/N 25 and 35. In addition, compost HA of C/N 15 had higher degree of humification and its structure was more stable.

The Identification and Genetic Characterization of Parechovirus Infection Among Pediatric Patients With Wide Clinical Spectrum in Chongqing, China.

Human parechoviruses (HPeVs) are important causes of infection in children. However, without a comprehensive and persistent surveillance, the epidemiology and clinical features of HPeV infection remain ambiguous. We performed a hospital-based surveillance study among three groups of pediatric patients with acute respiratory infection (Group 1), acute diarrhea (Group 2), and hand, foot and mouth disease (Group 3) in Chongqing, China, from 2009 to 2015. Among 10,212 tested patients, 707 (6.92%) were positive for HPeV, with the positive rates differing significantly among three groups (Group 1, 3.43%; Group 2, 14.94%; Group 3, 3.55%; P < 0.001). The co-infection with other pathogens was detected in 75.2% (531/707) of HPeV-positive patients. Significant negative interaction between HPeV and Parainfluenza virus (PIV) (P = 0.046, OR = 0.59, 95% CI = 0.34-0.98) and positive interactions between HPeV and Enterovirus (EV) (P = 0.015, OR = 2.28, 95% CI = 1.23-4.73) were identified. Among 707 HPeV-positive patients, 592 (83.73%) were successfully sequenced, and 10 genotypes were identified, with HPeV1 (n = 396), HPeV4 (n = 86), and HPeV3 (n = 46) as the most frequently seen. The proportion of genotypes differed among three groups (P < 0.001), with HPeV1 and HPeV4 overrepresented in Group 2 and HPeV6 overrepresented in Group 3. The spatial patterns of HPeV genotypes disclosed more close clustering of the currently sequenced strains than those from other countries/regions, although they were indeed mixed. Three main genotypes (HPeV1, HPeV3, and HPeV4) had shown distinct seasonal peaks, highlighting a bi-annual cycle of all HpeV and two genotypes (HPeV 1 and HPeV 4) with peaks in odd-numbered years and with peaks in even-numbered years HPeV3. Significantly higher HPeV1 viral loads were associated with severe diarrhea in Group 2 (P = 0.044), while associated with HPeV single infection than HPeV-EV coinfection among HFMD patients (P = 0.001). It's concluded that HPeV infection was correlated with wide clinical spectrum in pediatric patients with a high variety of genotypes determined. Still no clinical significance can be confirmed, which warranted more molecular surveillance in the future.

Fluorescent proteins as efficient tools for evaluating the surface PEGylation of silica nanoparticles.

Surface PEGylation is essential for preventing non-specific binding of biomolecules when silica nanoparticles are utilized for in vivo applications. Methods for installing poly(ethylene glycol) on a silica surface have been widely explored but varies from study to study. Because there is a lack of a satisfactory method for evaluating the properties of silica surface after PEGylation, the prepared nanoparticles are not fully characterized before use. In some cases, even non-PEGylated silica nanoparticles were produced, which is unfortunately not recognized by the end-user. In this work, a fluorescent protein was employed, which acts as a sensitive material for evaluating the surface protein adsorption properties of silica nanoparticles. Eleven different methods were systematically investigated for their reaction efficiency towards surface PEGylation. Results showed that both reaction conditions (including pH, catalyst) and surface functional groups of parent silica nanoparticles play critical roles in producing fully PEGylated silica nanoparticles. Great care needs to be taken in choosing the proper coupling chemistry for surface PEGylation. The data and method shown here will guarantee high-quality PEGylated silica nanoparticles to be produced and guide their applications in biology, chemistry, industry and medicine.

Prevalence and genetic characteristics of Saffold cardiovirus in China from 2009 to 2012.

The epidemiology and clinical features of the Saffold cardiovirus (SAFV) remain ambiguous. The present study was designed to systematically and intensively investigate the epidemiological features of SAFV in pediatric patients in China. Three cohorts of pediatric patients were recruited from 2009 to 2012. Cohort 1 comprised patients with acute respiratory tract infections. Cohort 2 comprised patients with diarrhea. Cohort 3 comprised hand, foot, and mouth disease (HFMD) patients. A total of 115 patients (1.6%) among 6052 (17/1647, 12/2013, and 86/2392 in cohorts 1, 2, and 3, respectively) were SAFV-positive. The samples from 82 SAFV-positive patients were successfully sequenced, and four genotypes were identified: 8 SAFV-1, 41 SAFV-2, 29 SAFV-3, and 4 SAFV-6. A significantly higher detection rate was found in the HFMD patients than in other two cohorts (both P <0.001). A higher frequency of severe clinical outcome and nervous system manifestation were also observed in the SAFV-positive HFMD patients. Additionally, 6 (3.5%) cerebrospinal fluid and 7 (2.2%) serum samples from the HFMD-associated encephalitis patients were SAFV-positive. Based on the VP1 sequences, all four genotypes displayed distinct geographical clustering. SAFV infection might be associated with a wide clinical spectrum and contribute to HFMD.

[Artificial propagation and embryonic development of Neolissochilus benasi].

From 2009 to 2011, luteinizing hormone releasing hormone analogue (LHRH-A2) mixed with domperidon (DOM) was successfully applied during the artificial propagation of Neolissochilus benasi. Totally, 60 females and 100 males were injected with the hormone mixture, resulting in 47 (78.3%) females and 92 (92.0%) males being successfully spawned. A total of 1,986-5 854 eggs were spawned per female with an egg diameter varying between 2.2-2.8 mm, and an average nucleus deviation rate of 73.2%. Sperm density, vitality and life span were 16.32±2.89×10(9)/mL, 60.6±3.2% and 70.2±5.3 s, respectively. On the whole, the embryonic development of N. benasi was similar to that of zebra fish-albeit relatively slower-lasting approximately 120 hours. The development itself can be divided into six discrete stages: zygote, cleavage, blastula, gastrula, segmentation and hatching. Results showed that the average hatching rate was 32.4%, with 86.5% of larvae surviving 45 days after hatching. During embryonic development, deformities commonly occurred on the mouth, chest, ocular region, especially in the spinal column. To try to attempt improving future breeding efforts, we provided a survey of the embryonic developmental difficulties of N. benasi using LHRH-A2 followed by several potential solutions, including providing suitable breeding conditions and minimizing capture stresses.

Circulation of Coxsackievirus A10 and A6 in hand-foot-mouth disease in China, 2009-2011.

Coxsackieviruses A10 (CV-A10) and A6 (CV-A6) have been associated with increasingly occurred sporadic hand-foot-mouth disease (HFMD) cases and outbreak events globally. However, our understanding of epidemiological and genetic characteristics of these new agents remains far from complete. This study was to explore the circulation of CV-A10 and CV-A6 in HFMD and their genetic characteristics in China. A hospital based surveillance was performed in three heavily inflicted regions with HFMD from March 2009 to August 2011. Feces samples were collected from children with clinical diagnosis of HFMD. The detection and genotyping of enteroviruses was performed by real-time PCR and sequencing of 5'UTR/VP1 regions. Phylogenetic analysis and selection pressure were performed based on the VP1 sequences. Logistic regression model was used to identify the effect of predominant enterovirus serotypes in causing severe HFMD. The results showed 92.0% of 1748 feces samples were detected positive for enterovirus, with the most frequently presented serotypes as EV-71 (944, 54.0%) and CV-A16 (451, 25.8%). CV-A10 and CV-A6 were detected as a sole pathogen in 82 (4.7%) and 44 (2.5%) cases, respectively. Infection with CV-A10 and EV-71 were independently associated with high risk of severe HFMD (OR = 2.66, 95% CI: 1.40-5.06; OR = 4.81, 95% CI: 3.07-7.53), when adjusted for age and sex. Phylogenetic analysis revealed that distinct geographic and temporal origins correlated with the gene clusters based on VP1 sequences. An overall ω value of the VP1 was 0.046 for CV-A10 and 0.047 for CV-A6, and no positively selected site was detected in VP1 of both CV-A10 and CV-A6, indicating that purifying selection shaped the evolution of CV-A10 and CV-A6. Our study demonstrates variety of enterovirus genotypes as viral pathogens in causing HFMD in China. CV-A10 and CV-A6 were co-circulating together with EV-71 and CV-A16 in recent years. CV-A10 infection might also be independently associated with severe HFMD.

Meta-analysis of randomized controlled trials to assess the effectiveness and safety of Free and Easy Wanderer Plus, a polyherbal preparation for depressive disorders.

Free and Easy Wanderer Plus (FEWP) is a polyherbal preparation which therapeutic benefits have been extensively evaluated in patients with various depressive disorders. The purpose of this meta-analysis was to assess the overall effectiveness and safety of FEWP. Following systematic review, a total of 14 high-quality randomized controlled trials (RCTs) were identified and included in the meta-analysis. Statistically greater treatment effects were found in FEWP monotherapy compared to placebo and in FEWP combined with conventional anti-depressants (CADs) compared to CADs alone. Patients taking FEWP alone and combined with CADs experienced fewer adverse events of dizziness, headache, dry mouth, nausea, and constipation compared to CADs alone. These data suggest that FEWP may be an effective herbal agent in treating depressive symptoms. The addition of FEWP also enhances antidepressant effects of CADs. FEWP may have a higher safety profile compared to CADs.

Plasmid-encapsulated polyethylene glycol-grafted polyethylenimine nanoparticles for gene delivery into rat mesenchymal stem cells.

BACKGROUND: Mesenchymal stem cell transplantation is a promising method in regenerative medicine. Gene-modified mesenchymal stem cells possess superior characteristics of specific tissue differentiation, resistance to apoptosis, and directional migration. Viral vectors have the disadvantages of potential immunogenicity, carcinogenicity, and complicated synthetic procedures. Polyethylene glycol-grafted polyethylenimine (PEG-PEI) holds promise in gene delivery because of easy preparation and potentially targeting modification. METHODS: A PEG8k-PEI25k graft copolymer was synthesized. Agarose gel retardation assay and dynamic light scattering were used to determine the properties of the nanoparticles. MTT reduction, wound and healing, and differentiation assays were used to test the cytobiological characteristics of rat mesenchymal stem cells, fluorescence microscopy and flow cytometry were used to determine transfection efficiency, and atomic force microscopy was used to evaluate the interaction between PEG-PEI/plasmid nanoparticles and mesenchymal stem cells. RESULTS: After incubation with the copolymer, the bionomics of mesenchymal stem cells showed no significant change. The mesenchymal stem cells still maintained high viability, resettled the wound area, and differentiated into adipocytes and osteoblasts. The PEG-PEI completely packed plasmid and condensed plasmid into stable nanoparticles of 100-150 nm diameter. After optimizing the N/P ratio, the PEG-PEI/plasmid microcapsules delivered plasmid into mesenchymal stem cells and obtained an optimum transfection efficiency of 15%-21%, which was higher than for cationic liposomes. CONCLUSION: These data indicate that PEG-PEI is a valid gene delivery agent and has better transfection efficiency than cationic liposomes in mesenchymal stem cells.