Local generation of hydrogen for enhanced photothermal therapy.

By delivering the concept of clean hydrogen energy and green catalysis to the biomedical field, engineering of hydrogen-generating nanomaterials for treatment of major diseases holds great promise. Leveraging virtue of versatile abilities of Pd hydride nanomaterials in high/stable hydrogen storage, self-catalytic hydrogenation, near-infrared (NIR) light absorption and photothermal conversion, here we utilize the cubic PdH0.2 nanocrystals for tumour-targeted and photoacoustic imaging (PAI)-guided hydrogenothermal therapy of cancer. The synthesized PdH0.2 nanocrystals have exhibited high intratumoural accumulation capability, clear NIR-controlled hydrogen release behaviours, NIR-enhanced self-catalysis bio-reductivity, high NIR-photothermal effect and PAI performance. With these unique properties of PdH0.2 nanocrystals, synergetic hydrogenothermal therapy with limited systematic toxicity has been achieved by tumour-targeted delivery and PAI-guided NIR-controlled release of bio-reductive hydrogen as well as generation of heat. This hydrogenothermal approach has presented a cancer-selective strategy for synergistic cancer treatment

Optical and Gamma-Ray Variability Behaviors of 3C 454.3 from 2006 to 2011

We present our photometric monitoring of a flat spectrum radio quasar (FSRQ) 3C 454.3 at Yunnan observatories from 2006 to 2011. We find that the optical color of 3C 454.3 shows obvious redder-when-brighter trend, which reaches a saturation stage when the source is brighter than 15.15 mag at V band. We perform a simulation with multiple values of disk luminosity and spectral index to reproduce the magnitude-color diagram. The results show that the contamination caused by the disk radiation alone is difficult to produce the observed color variability. The variability properties during the outburst in December 2009 are also compared with $\gamma$-ray data derived from Fermi $\gamma$-ray space telescope. The flux variation of these two bands follow a linear relation with $F_{\gamma} \propto F_R^{1.14\pm0.07}$, which provides an observational evidence for external Compton process in 3C 454.3. Meanwhile, this flux correlation indicates that electron injection is the main mechanism for variability origin. We also explore the variation of the flux ratio $F_{\gamma}/F_R$ and the detailed structures in the lightcurves, and discuss some possible origins for the detailed variability behaviors.Comment: accepted for publication in The Astrophysical Journal, 5 figures, 2 table

Thermokinetic profile of NDM-1 and its inhibition by small carboxylic acids

The New Delhi metallo-β-lactamase (NDM-1) is an important clinical target for antimicrobial research, but there are insufficient clinically useful inhibitors and the details of NDM-1 enzyme catalysis remain unclear. The aim of this work is to provide a thermodynamic profile of NDM-1 catalysed hydrolysis of β-lactams using an isothermal titration calorimetry (ITC) approach and to apply this new method to the identification of new low-molecular-weight dicarboxylic acid inhibitors. The results reveal that hydrolysis of penicillin G and imipenem by NDM-1 share the same thermodynamic features with a significant intrinsic enthalpy change and the release of one proton into solution, while NDM-1 hydrolysis of cefazolin exhibits a different mechanism with a smaller enthalpy change and the release of two protons. The inhibitory constants of four carboxylic acids are found to be in the micromolar range. The compounds pyridine-2,6-dicarboxylic acid and thiazolidine-2,4-dicarboxylic acid show the best inhibitory potency and are confirmed to inhibit NDM-1 using a clinical strain of Escherichia coli. The pyridine compound is further shown to restore the susceptibility of this E. coli strain to imipenem, at an inhibitor concentration of 400 μM, while the thiazoline compound also shows a synergistic effect with imipenem. These results provide valuable information to enrich current understanding on the catalytic mechanism of NDM-1 and to aid the future optimisation of β-lactamase inhibitors based on these scaffolds to tackle the problem of antibiotic resistance

Genetic Variants of IDE-KIF11-HHEX at 10q23.33 Associated with Type 2 Diabetes Risk: A Fine-Mapping Study in Chinese Population

Background: Genome-wide association studies (GWAS) in populations of European ancestry have mapped a type 2 diabetes susceptibility region to chromosome 10q23.33 containing IDE, KIF11 and HHEX genes (IDE-KIF11-HHEX), which has also been replicated in Chinese populations. However, the functional relevance for genetic variants at this locus is still unclear. It is critical to systematically assess the relationship of genetic variants in this region with the risk of type 2 diabetes. Methodology/Principal Findings: A fine-mapping study was conducted by genotyping fourteen tagging single-nucleotide polymorphisms (SNPs) in a 290-kb linkage disequilibrium (LD) region using a two-stage case-control study of type 2 diabetes in a Chinese Han population. Suggestive associations (P,0.05) observed from 1,200 cases and 1,200 controls in the first stage were further replicated in 1,725 cases and 2,081 controls in the second stage. Seven tagging SNPs were consistently associated with type 2 diabetes in both stages (P,0.05), with combined odds ratios (ORs) ranging from 1.14 to 1.33 in the combined analysis. The most significant locus was rs7923837 [OR = 1.33, 95 % confidence interval (CI): 1.21–1.47] at the 39-flanking region of HHEX gene. SNP rs1111875 was found to be another partially independent locus (OR = 1.23, 95% CI: 1.13–1.35) in this region that was associated with type 2 diabetes risk. A cumulative effect of rs7923837 and rs1111875 was observed with individuals carrying 1, 2, and 3 or 4 risk alleles having a 1.27, 1.44, and 1.73-fold increased risk, respectively, for type 2 diabetes (P for trend = 4.1E-10)

Study on long-term performance evaluation of auditory and speech ability in cochlear implant in congenital deaf children with cochlear nerve deficiency after cochlear implantation

Objective·To evaluate the long-term performance and influencing factors of auditory and speech abilities, and social-life abilities in congenital deaf children with cochlear nerve deficiency (CND) after cochlear implant (CI) surgery.Methods·Twenty-one CND children with CI implantation in Shanghai Ninth People′s Hospital, Shanghai Jiao Tong University School of Medicine were assigned to CND group, and twenty children with extremely severe sensorineural hearing loss with normal inner ear structure matching implantation age and CI use time of the CND group were selected as control group. The aided hearing threshold, Infant-toddler Meaningful Auditory Integration Scale (IT-MAIS), LittlEARS Auditory Questionnaire (LEAQ), Categories of Auditory Performance-Ⅱ (CAP-Ⅱ), Meaningful Use of Speech Scale (MUSS), Speech Intelligibility Rating (SIR), closed and open disyllabic speech recognition test, and speech intelligibility test were used to hierarchically evaluate the subjects′ auditory and verbal abilities, and the Infant-junior Middle School Student′s Social Life Ability Scale (S-M Scale) was used to assess the subjects′ social-life ability.Results·The average aided hearing threshold of each frequency point in the CND group was significantly worse than that of the control group (all P<0.05). In the CND group, 90.5% of children′s aided hearing threshold of all frequencies entered the Chinese banana map. The auditory and speech abilities of the CND group were worse than those of the control group, and the significant differences between the two groups were found in the results of IT-MAIS, CAP-Ⅱ, MUSS, SIR, and closed and open disyllabic speech recognition (all P<0.05), but not in LEAQ. The social-life ability of the CND group was worse than that of the control group, and the difference was statistically significant (P<0.05). There was no correlation between implantation age, usage time of CI, auditory and language rehabilitation time, and auditory and speech ability of the CND group.Conclusion·CI is an effective auditory intervention method for children with CND, but their average auditory and speech abilities and social-life abilities are significantly behind those of CI users with normal inner ear structure. Therefore, for CND children, individualized communication strategies and rehabilitation training methods should be emphasized, and the cultivation of social-life ability and psychological guidance should be strengthened

Misuse of Statistical Methods in 10 Leading Chinese Medical Journals in 1998 and 2008

Statistical methods are vital to biomedical research. Our aim was to find out whether progress has been made in the last decade in the use of statistical methods in Chinese medical research. We reviewed 10 leading Chinese medical journals published in 1998 and in 2008. Regarding statistical methods, using a multiple t-test for multiple group comparison was the most common error in the t-test in both years, which significantly decreased in 2008. In contingency tables, no significant level adjustment for multiple comparison significantly decreased in 2008. In ANOVA, over a quarter of articles misused the method of multiple pair-wise comparison in both years, and no significant difference was seen between the two years. In the rank transformation nonparametric test, the error of using multiple pair-wise comparison for multiple group comparison became less common. Many mistakes were found in the randomised controlled trial (56.3% in 1998; 67.9% in 2008), non- randomised clinical trial (57.3%; 58.6%), basic science study (72.9%; 65.5%), case study or case series study (48.4%; 47.2%), and cross-sectional study (57.1%; 44.2%). Progress has been made in the use of statistical methods in Chinese medical journals, but much is yet to be done