A Reversible Fluorescent Probe for In Situ Monitoring Redox Imbalance during Mitophagy.

Mitophagy is the lysosome-dependent degradation of damaged and dysfunctional mitochondria, which is closely associated with H2O2-related redox imbalance and pathological processes. However, development of fast-responding and highly sensitive reversible fluorescent probes for monitoring of mitochondrial H2O2 dynamics is still lacking. Herein, we report a reversible fluorescent probe (M-HP) that enables real-time imaging of H2O2-related redox imbalance. In vitro studies demonstrated that M-HP had a rapid response and high sensitivity to the H2O2/GSH redox cycle, with a detection limit of 17 nM for H2O2. M-HP was applied to imaging of H2O2 fluctuation in living cells with excellent reversibility and mitochondrial targeting. M-HP reveals an increase in mitochondrial H2O2 under lipopolysaccharide stimulation and a decrease in H2O2 following the combined treatment with rapamycin. This suggests that the level of oxidative stress is significantly suppressed after the enhancement of mitophagy. The rationally designed M-HP offers a powerful tool for understanding redox imbalance during mitophagy.

Brain-targeted Near-Infrared Nanobeacon for In Situ Monitoring H2S Fluctuation during Epileptic Seizures.

Epilepsy is a neurological brain disease, and its recurrent seizures are related to the reductive substance-powered antioxidant defense system (ADS). However, until now, there has been no report on the study of in situ antioxidant fluctuation during epilepsy of varying severity. In this work, hydrogen sulfide (H2S) was selected as the model target, a H2S-responsive near-infrared fluorophore was designed and synthesized, and an amphiphilic molecule was synthesized and modified with angiopep-2 peptide at its hydrophilic terminus. A nanobeacon termed as BFPP was prepared by the formation of micelles with the package of the fluorophore. The nanobeacon was sensitive to H2S, with a low detection limit of 17 nM. The H2S fluctuation in cells can be monitored by fluorescence imaging. In addition, angiopep-2 peptide at the surface of BFPP helps it cross the blood-brain barrier, and near-infrared fluorescence improves in vivo imaging. BFPP revealed that H2S was at a moderate level in the normal brain, but its level was obviously elevated during mild epilepsy because of the activation of the ADS while significantly suppressed during severe epilepsy due to neuronal damage. This approach is generally accessible for other targets by altering the responsive fluorophore, with significance for in situ analysis of brain pathology.

Extracting Effective Image Attributes with Refined Universal Detection.

Recently, image attributes containing high-level semantic information have been widely used in computer vision tasks, including visual recognition and image captioning. Existing attribute extraction methods map visual concepts to the probabilities of frequently-used words by directly using Convolutional Neural Networks (CNNs). Typically, two main problems exist in those methods. First, words of different parts of speech (POSs) are handled in the same way, but non-nominal words can hardly be mapped to visual regions through CNNs only. Second, synonymous nominal words are treated as independent and different words, in which similarities are ignored. In this paper, a novel Refined Universal Detection (RUDet) method is proposed to solve these two problems. Specifically, a Refinement (RF) module is designed to extract refined attributes of non-nominal words based on the attributes of nominal words and visual features. In addition, a Word Tree (WT) module is constructed to integrate synonymous nouns, which ensures that similar words hold similar and more accurate probabilities. Moreover, a Feature Enhancement (FE) module is adopted to enhance the ability to mine different visual concepts in different scales. Experiments conducted on the large-scale Microsoft (MS) COCO dataset illustrate the effectiveness of our proposed method.

Efficacy, safety, and immunogenicity of an enterovirus 71 vaccine in China.

BACKGROUND: Enterovirus 71 (EV71) is one of the major causative agents of outbreaks of hand, foot, and mouth disease or herpangina worldwide. This phase 3 trial was designed to evaluate the efficacy, safety, and immunogenicity of an EV71 vaccine. METHODS: We conducted a randomized, double-blind, placebo-controlled, multicenter trial in which 10,007 healthy infants and young children (6 to 35 months of age) were randomly assigned in a 1:1 ratio to receive two intramuscular doses of either EV71 vaccine or placebo, 28 days apart. The surveillance period was 12 months. The primary end point was the occurrence of EV71-associated hand, foot, and mouth disease or herpangina. RESULTS: During the 12-month surveillance period, EV71-associated disease was identified in 0.3% of vaccine recipients (13 of 5041 children) and 2.1% of placebo recipients (106 of 5028 children) in the intention-to-treat cohort. The vaccine efficacy against EV71-associated hand, foot, and mouth disease or herpangina was 94.8% (95% confidence interval [CI], 87.2 to 97.9; P<0.001) in this cohort. Vaccine efficacies against EV71-associated hospitalization (0 cases vs. 24 cases) and hand, foot, and mouth disease with neurologic complications (0 cases vs. 8 cases) were both 100% (95% CI, 83.7 to 100 and 42.6 to 100, respectively). Serious adverse events occurred in 111 of 5044 children in the vaccine group (2.2%) and 131 of 5033 children in the placebo group (2.6%). In the immunogenicity subgroup (1291 children), an anti-EV71 immune response was elicited by the two-dose vaccine series in 98.8% of participants at day 56. An anti-EV71 neutralizing antibody titer of 1:16 was associated with protection against EV71-associated hand, foot, and mouth disease or herpangina. CONCLUSIONS: The EV71 vaccine provided protection against EV71-associated hand, foot, and mouth disease or herpangina in infants and young children. (Funded by Sinovac Biotech; ClinicalTrials.gov number, NCT01507857.).

The Uncommon Channel-Based Ln-MOFs for Highly Selective Fe3+ Detection and Superior Rhodamine†B Adsorption.

Two new isostructural 3D lanthanide-organic frameworks [H2 N(Me)2 ] [Ln3 (OH)(bpt)3 (H2 O)3 ] (DMF)2 ⋅(H2 O)4 (1-Ln; Ln=Sm and Eu) with a 1D channel (25 Å) have been successfully assembled from the rare trinuclear [Ln3 (OH)(COO)9 ] clusters and biphenyl-3,4',5-tricarboxylic acid (H3 bpt) and exhibit high stability towards water in the pH range 3-10. MOF 1-Eu is a promising luminescent probe for sensing Fe3+ in aqueous solution and is also selective towards rhodamine B (RhB) with a superior adsorption capacity of 735 mg g-1 , which is the highest among the reported Ln-MOFs for RhB removal so far. Periodic DFT calculations further confirmed the selective adsorption of rhodamine B over other dyes.

Immunogenicity, safety, and immune persistence of a novel inactivated human enterovirus 71 vaccine: a phase II, Randomized, double-blind, placebo-controlled Trial.

BACKGROUND: Vaccination is considered a top priority for the control of human enterovirus 71 (EV71) infection outbreaks. METHODS: On the basis of phase I trial results, we conducted a double-blind, randomized, controlled trial to evaluate the optimal dose, immunogenicity, safety and immune persistence of the vaccine. A total of 480 healthy infants were randomly assigned to receive 2 injections of 100 U of vaccine, 200 U of vaccine, 400 U of vaccine, or placebo. Solicited adverse events (AEs) within 7 days and unsolicited AEs within 28 days after each vaccination were collected for safety evaluation. Blood samples were collected for neutralizing antibody assay. RESULTS: EV71 vaccine was well tolerated, and no dose-related safety concerns were observed. Two doses of the vaccine yielded seropositivity frequencies of 92.3%, 95.9%, and 99.0% (with titers ≥1:8) in the 100 U, 200 U, and 400 U groups, respectively. Geometric mean titers measured by neutralizing antibody assay increased to 60.2 (95% confidence interval [CI], 41.9-86.4), 72.8 (95% CI, 50.8-104.3), and 252.1 (95% CI, 180.8-351.6) for the 100 U, 200 U, and 400 U groups, respectively. The dose-response relationship, with the 400 U dose showing higher immunogenicity than the 100 U and 200 U doses, remained until 13 months after the second vaccination, despite waning antibody levels. CONCLUSIONS: The 400 U dose was recommended as the optimal dose for the phase III trial because of its good safety profile and higher immunogenicity.

Bifunctional CoFe/HZSM-5 catalysts orient CO2 hydrogenation towards liquid hydrocarbons.

Converting CO2 to liquid (C5+) hydrocarbons remains a significant hurdle. Our study shows that CoFe/HZSM-5 boosts C5+ selectivity to 73.4%, up from 59% for Fe/HZSM-5. This study highlights the pivotal roles of zeolite acidity and catalyst proximity in this improvement. These insights pave the way for more effective CO2 utilization.

A rapid immune response to 2009 influenza A(H1N1) vaccines in adults: a randomized, double-blind, controlled trial.

A double-blind, randomized, controlled trial involving 706 adults was conducted to evaluate the immunogenicity and safety of different dosages of whole-virion or split-virion H1N1 influenza vaccines with or without aluminum adjuvant. A rapid and strong immune response was induced at day 14 after the first injection. The seroprotection rates ranged from 72.7% (95% confidence interval [CI], 62.7%-81.1%) for 5-microg whole-virion aluminum formulation to 97.0% (95% CI, 90.9%-99.7%) for 30-microg split-virion nonaluminum formulation. All formulations were well tolerated. The incidences of mild, moderate, and severe reactions were 71 (10.1%), 15 (2.1%), and 1 (0.1%) of 706 reactions, respectively. The 15-microg split-virion formulation had the best immunogenicity and safety.

Oxidase-mimicking activity of perovskite LaMnO3+δ nanofibers and their application for colorimetric sensing.

Nanomaterials with ABX3-type perovskite structure have attracted considerable and increasing attention due to their unique physical and chemical properties as well as promising applications in various fields. In this work, we have developed a simple electrospinning followed by a calcination process to prepare ABO3-type perovskite LaMnO3+δ nanofibers as efficient oxidase mimics for the detection of l-cysteine. The oxidase-like catalytic activity of the prepared LaMnO3+δ nanofibers is heavily dependent on the calcination temperature which results in different sizes of the LaMnO3+δ crystals and their crystallinity, and the maximum activity is achieved at the calcination temperature of 700 °C. Based on the high oxidase-like catalytic activity of the as-prepared perovskite LaMnO3+δ nanofibers, a simple and accurate colorimetric detection method towards l-cysteine has been developed. The detection limit is as low as 109.8 nM and an excellent selectivity for l-cysteine detection with common substances in human blood as interferents is also achieved. In addition, the LaMnO3+δ nanofibers can be retained as a monolithic membrane after the calcination process, making them an oxidase mimic for on-demand colorimetric sensing. This work reveals the promising prospects for the perovskite LaMnO3+δ materials in biosensing, medical diagnosis, food safety and environmental monitoring.

Five-year antibody persistence in children after one dose of inactivated or live attenuated hepatitis A vaccine.

In China, both inactivated hepatitis A (HA) vaccine and live attenuated HA vaccine are available. We conducted a trial to evaluate 5-year immune persistence induced by one dose of inactivated or live attenuated HA vaccines in children. Subjects with no HA vaccination history had randomly received one dose of inactivated or live attenuated HA vaccine at 18-60 months of age. Anti-HAV antibody concentrations were measured before vaccination and at the first, second, and fifth year after vaccination. Suspected cases of hepatitis A were monitored during the study period. A total of 332 subjects were enrolled and 182 provided evaluable serum samples at all planned time points. seropositive rate at 5 y was 85.9% in the inactivated HA vaccine group and 90.7% in the live attenuated HA vaccine group. GMCs were 76.3% mIU/ml (95% CI: 61.7 - 94.4) and 66.8mIU/ml (95% CI: 57.8 - 77.3), respectively. No significant difference in antibody persistence between 2 groups was found. No clinical hepatitis A case was reported. A single dose of an inactivated or live attenuated HA vaccine at 18-60 months of age resulted in high HAV seropositive rate and anti-HAV antibody concentrations that lasted for at least 5 y.

Manipulation the behavior of supramolecular hydrogels of α-cyclodextrin/star-like block copolymer/carbon-based nanomaterials.

A new supramolecular hydrogel self-assembled between α-cyclodextrin (α-CD) and a star-like block copolymer AE73 was prepared. The cooperation effect of complexation of poly-(ethylene oxide) (PEO) segments with α-CD and the hydrophobic interaction between poly-(propylene oxide) (PPO) blocks resulted in the formation of the supramolecular hydrogel with a strong macromolecular network. Then two kinds of carbon materials (graphene and graphene oxide) were successfully incorporated into the above α-CD/AE73 hydrogel to further enhance the mechanical properties. The native hydrogel, as well as hybrid hydrogels, have been thoroughly characterized by using various microscopic techniques, including transmission electron microscopy (TEM), field emission scanning electron microscopy (FE-SEM), Fourier transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), thermogravimetric analysis (TGA). Our main purpose is to ascertain whether the properties of the obtained gels depend on these architectures. Interestingly, the phase behavior, the morphology and the mechanical strength of the native hydrogel can be successfully modulated by incorporating graphene and graphene oxide. Taking into account that both PEO/PPO copolymers and α-CD seem to be biocompatible, these gels can be promising for biomedical applications.

[Observation and comparison of the flowers of Pogostemon cablin from different habitats].

The present work is concerned in the observation and comparison among the flowers of Pogostemon cablin (Blanco) Benth. from 3 different habitats by microscopical identification and electron microscopy scanning. The results provided scientific basis for recognition and distinction of Pogostemon cablin varieties.

Optimal vaccination strategies for 2009 pandemic H1N1 and seasonal influenza vaccines in humans.

A randomized clinical trial was conducted to assess whether the immunogenicity of seasonal and pandemic (H1N1/09) influenza vaccines is affected by the order of vaccine administration. 151 healthy adult volunteers were randomized into three groups. All groups received one dose (15 µg haemagglutinin) each of a pandemic H1N1 vaccine and a seasonal trivalent vaccine. Group 1 received the pandemic H1N1 vaccine first, followed by the seasonal vaccine 21 days later. Group 2 received vaccinations in vice versa and Group 3 received both vaccines simultaneously. Post-vaccination blood samples were collected to determine the immunogenicity by hemagglutination-inhibition (HI), microneutralization (MN), and B cell ELISPOT assays. All three vaccination strategies were well-tolerated and generated specific immune responses. However, we found a significant difference in magnitude of antibody responses to pandemic H1N1 between the three groups. Pre- or co-vaccination with the seasonal flu vaccine led to a significant reduction by 50% in HI titre to pandemic H1N1 virus after pandemic vaccination. Pre- or co-vaccination of pandemic H1N1 vaccine had no effect on seasonal flu vaccination. MN and ELISPOT assays showed a similar effect. Vaccination with pandemic H1N1 vaccine first is recommended to avoid an associated inhibitory effect by the seasonal trivalent flu vaccine.

Preparation and characterization of SARS in-house reference antiserum.

A reference antiserum for SARS is in urgent need in the development of SARS vaccine and other serological test of SARS research. Convalescent serum was collected from clinical confirmed patient. ELISA, Western-blotting and neutralization assay detected specific antibody against SARS coronavirus. This antiserum was prepared as in-house reference antiserum, freeze-dried and sealed in ampoules. The potency of this reference antiserum is defined to be 52.7 U after extensive calibration. Further, collaborative studies for the evaluation of this serum are needed in order to satisfy the requirements for international reference antiserum.