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1.  Corticothalamic Axons Are Essential for Retinal Ganglion Cell Axon Targeting to the Mouse Dorsal Lateral Geniculate Nucleus 
The Journal of Neuroscience  2016;36(19):5252-5263.
Retinal ganglion cells (RGCs) relay information about the outside world to multiple subcortical targets within the brain. This information is either used to dictate reflexive behaviors or relayed to the visual cortex for further processing. Many subcortical visual nuclei also receive descending inputs from projection neurons in the visual cortex. Most areas receive inputs from layer 5 cortical neurons in the visual cortex but one exception is the dorsal lateral geniculate nucleus (dLGN), which receives layer 6 inputs and is also the only RGC target that sends direct projections to the cortex. Here we ask how visual system development and function changes in mice that develop without a cortex. We find that the development of a cortex is essential for RGC axons to terminate in the dLGN, but is not required for targeting RGC axons to other subcortical nuclei. RGC axons also fail to target to the dLGN in mice that specifically lack cortical layer 6 projections to the dLGN. Finally, we show that when mice develop without a cortex they can still perform a number of vision-dependent tasks.
SIGNIFICANCE STATEMENT The dorsal lateral geniculate nucleus (dLGN) is a sensory thalamic relay area that receives feedforward inputs from retinal ganglion cells (RGCs) in the retina, and feed back inputs from layer 6 neurons in the visual cortex. In this study we examined genetically manipulated mice that develop without a cortex or without cortical layer 6 axonal projections, and find that RGC axons fail to project to the dLGN. Other RGC recipient areas, such as the superior colliculus and suprachiasmatic nucleus, are targeted normally. These results provide support for a new mechanism of target selection that may be specific to the thalamus, whereby descending cortical axons provide an activity that promotes feedforward targeting of RGC axons to the dLGN.
doi:10.1523/JNEUROSCI.4599-15.2016
PMCID: PMC4863061  PMID: 27170123
axon-targeting; cortex; dLGN; retina; target selection; visual system
2.  Increased risk of vertebral fracture in patients with rheumatoid arthritis 
Medicine  2016;95(45):e5262.
Abstract
The relationship between rheumatoid arthritis and risk of vertebral fracture has been reported by several observational studies. However, there is no higher-level evidence study, such as meta-analysis, that has investigated the relationship, and its mechanisms are not yet fully clear. This meta-analysis aimed to provide a summary of an observational study of the relationship between rheumatoid arthritis and the risk of vertebral fractures.
Relevant studies were identified by searching PubMed and EMBASE databases (up to August 1, 2016). We included published observational studies (cohort or case-control design) evaluating the relationship between rheumatoid arthritis and the risk of vertebral fractures. Two reviewers searched and abstracted the data independently. Relative risks (RRs) with 95% confidence intervals (CIs) were used throughout the whole analysis.
Seven observational studies (2 cohort studies, 2 nested case-control studies, and 3 case-control studies) were included in this meta-analysis. The results showed that the pooled RR of vertebral fracture for individuals with rheumatoid arthritis was 2.34 (95% CI 2.05–2.63, I2 = 35.4%, P for heterogeneity = 0.16). Further subgroup analysis by sex showed that the pooled RRs for both women and men, and only women were 2.14 (95% CI 1.47–2.8, I2 = 48.5%, P for heterogeneity = 0.12) and 2.39 (95% CI 2.07–2.70, I2 = 34%, P for heterogeneity = 0.22), respectively. Subgroup analysis by study design showed that the pooled RRs for cohort studies, nested case-control studies, and case-control studies were 2.31 (95% CI 1.95–2.67, I2 = 4.8%, P for heterogeneity = 0.31), 1.89 (95% CI 1.01–2.77, I2 = 72.1%, P for heterogeneity = 0.06), and 2.62 (95% CI 2.04–3.91, I2 = 26.1%, P for heterogeneity = 0.26), respectively.
Based on our meta-analysis, rheumatoid arthritis should be regarded as an independent risk factor of vertebral fracture. Further studies are needed to institute prevention and treatment strategies.
doi:10.1097/MD.0000000000005262
PMCID: PMC5106053  PMID: 27828847
meta-analysis; rheumatoid arthritis; risk; vertebral fracture
3.  The efficacy of daily chlorhexidine bathing for preventing healthcare-associated infections in adult intensive care units 
Background/Aims
Healthcare-associated infections (HAIs) in critically ill patients with prolonged length of hospital stay and increased medical costs. The aim of this study is to assess whether daily chlorhexidine gluconate (CHG) bathing will significantly reduce the rates of HAIs in adult intensive care units (ICUs).
Methods
PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials were systematically searched until December 31, 2014 to identify relevant studies. Two authors independently reviewed and extracted data from included studies. All data was analyzed by Review Manager version 5.3.
Results
Fifteen studies including three randomized controlled trials and 12 quasi-experimental studies were available in this study. The outcomes showed that daily CHG bathing were associated with significant reduction in the rates of primary outcomes: catheter-related bloodstream infection (risk ratio [RR], 0.44; 95% confidence interval [CI], 0.32 to 0.63; p < 0.00001), catheter-associated urinary tract infection (RR, 0.68; 95% CI, 0.52 to 0.88; p = 0.004), ventilator-associated pneumonia (RR, 0.73; 95% CI, 0.57 to 0.93; p = 0.01), acquisition of methicillin-resistant Staphylococcus aureus (RR, 0.78; 95% CI, 0.68 to 0.91; p = 0.001) and vancomycin-resistant Enterococcus (RR, 0.56; 95% CI, 0.31 to 0.99; p = 0.05).
Conclusions
Our study suggests that the use of daily CHG bathing can significantly prevent HAIs in ICUs. However, more well-designed studies are needed to confirm these findings.
doi:10.3904/kjim.2015.240
PMCID: PMC5094930  PMID: 27048258
Chlorhexidine gluconate; Bathing; Infection; Intensive care units
4.  A CRISPR Dropout Screen Identifies Genetic Vulnerabilities and Therapeutic Targets in Acute Myeloid Leukemia 
Cell Reports  2016;17(4):1193-1205.
Summary
Acute myeloid leukemia (AML) is an aggressive cancer with a poor prognosis, for which mainstream treatments have not changed for decades. To identify additional therapeutic targets in AML, we optimize a genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) screening platform and use it to identify genetic vulnerabilities in AML cells. We identify 492 AML-specific cell-essential genes, including several established therapeutic targets such as DOT1L, BCL2, and MEN1, and many other genes including clinically actionable candidates. We validate selected genes using genetic and pharmacological inhibition, and chose KAT2A as a candidate for downstream study. KAT2A inhibition demonstrated anti-AML activity by inducing myeloid differentiation and apoptosis, and suppressed the growth of primary human AMLs of diverse genotypes while sparing normal hemopoietic stem-progenitor cells. Our results propose that KAT2A inhibition should be investigated as a therapeutic strategy in AML and provide a large number of genetic vulnerabilities of this leukemia that can be pursued in downstream studies.
Graphical Abstract
Highlights
•Optimized CRISPR platform for identification of genome-wide genetic vulnerabilities•Catalog of genetic vulnerabilities in acute myeloid leukemia cell lines•KAT2A inhibition induces myeloid differentiation and apoptosis•KAT2A inhibition arrests the growth of primary AML cells, but not of normal progenitors
Tzelepis et al. optimize a CRISPR-Cas9-based platform for the performance of genome-wide recessive screens and apply it to identify genetic vulnerabilities of human AML cells. They identify several known therapeutic targets including BRD4, DOT1L, and MEN1, and numerous additional candidates. They provide data proposing KAT2A as a potential therapeutic target.
doi:10.1016/j.celrep.2016.09.079
PMCID: PMC5081405  PMID: 27760321
CRISPR; genetic screen; genetic vulnerability; acute myeloid leukemia; AML; KAT2A; MB-3
5.  Hole‐Accepting‐Ligand‐Modified CdSe QDs for Dramatic Enhancement of Photocatalytic and Photoelectrochemical Hydrogen Evolution by Solar Energy 
Advanced Science  2015;3(4):1500282.
Solar H2 evolution of CdSe QDs can be significantly enhanced simply by introducing a suitable hole‐accepting‐ligand for achieving efficient hole extraction and transfer at the nanoscale interfaces, which opens an effective pathway for dissociation of excitons to generate long‐lived charge separation, thus improving the solar‐to‐fuel conversion efficiency.
doi:10.1002/advs.201500282
PMCID: PMC5063123  PMID: 27774400
artificial photosynthesis; charge transfer; H2 evolution; hole transfer; ligand‐modified QDs
6.  Do Peers Matter? Resistance to Peer Influence as a Mediator between Self-Esteem and Procrastination among Undergraduates 
Frontiers in Psychology  2016;7:1529.
This study examined the relationship between self-esteem and procrastination and the mediating role of resistance to peer influence (RPI) on this relationship among undergraduates. One hundred and ninety-nine Chinese undergraduate students completed the measures of procrastination, RPI, and self-esteem. Structural Equation Modeling analyses indicated that self-esteem was negatively related to procrastination, and RPI acted as a mediator of this relationship. The results suggest that the peer may be a key to understanding procrastination among undergraduates. Implications for future research and limitations of the current study are discussed.
doi:10.3389/fpsyg.2016.01529
PMCID: PMC5045931  PMID: 27752248
procrastination; self-esteem; resistance to peer influence
7.  Salvage interstitial brachytherapy based on computed tomography for recurrent cervical cancer after radical hysterectomy and adjuvant radiation therapy: case presentations and introduction of the technique 
Purpose
Locally recurring cervical cancer after surgery and adjuvant radiotherapy remains a major therapeutic challenge. This paper presents a new therapeutic technique for such patients: interstitial brachytherapy (BT) guided by real-time three-dimensional (3D) computed tomography (CT).
Material and methods
Sixteen patients with recurrent cervical cancer after radical surgery and adjuvant external-beam radiotherapy (EBRT) were included in this study. These patients underwent high-dose-rate (HDR) interstitial BT with free-hand placement of metal needles guided by real-time 3D-CT. Six Gy in 6 fractions were prescribed for the high-risk clinical target volume (HR-CTV). D90 and D100 for HR-CTV of BT, and the cumulative D2cc for the bladder, rectum, and sigmoid, including previous EBRT and present BT were analyzed. Treatment-related complications and 3-month tumor-response rates were investigated.
Results
The mean D90 value for HR-CTV was 52.5 ± 3.3 Gy. The cumulative D2cc for the bladder, rectum, and sigmoid were 85.6 ± 5.8, 71.6 ± 6.4, and 69.6 ± 5.9 Gy, respectively. The mean number of needles was 6.1 ± 1.5, with an average depth of 3.5 ± 0.9 cm for each application. Interstitial BT was associated with minor complications and passable tumor-response rate.
Conclusions
Interstitial BT guided by real-time 3D-CT for recurrent cervical cancer results in good dose-volume histogram (DVH) parameters. The current technique may be clinically feasible. However, long-term clinical outcomes should be further investigated.
doi:10.5114/jcb.2016.63192
PMCID: PMC5116451  PMID: 27895683
cervical cancer; computed tomography; interstitial brachytherapy; recurrence
8.  Unusual lattice vibration characteristics in whiskers of the pseudo-one-dimensional titanium trisulfide TiS3 
Nature Communications  2016;7:12952.
Transition metal trichalcogenides form a class of layered materials with strong in-plane anisotropy. For example, titanium trisulfide (TiS3) whiskers are made out of weakly interacting TiS3 layers, where each layer is made of weakly interacting quasi-one-dimensional chains extending along the b axis. Here we establish the unusual vibrational properties of TiS3 both experimentally and theoretically. Unlike other two-dimensional systems, the Raman active peaks of TiS3 have only out-of-plane vibrational modes, and interestingly some of these vibrations involve unique rigid-chain vibrations and S–S molecular oscillations. High-pressure Raman studies further reveal that the AgS–S S-S molecular mode has an unconventional negative pressure dependence, whereas other peaks stiffen as anticipated. Various vibrational modes are doubly degenerate at ambient pressure, but the degeneracy is lifted at high pressures. These results establish the unusual vibrational properties of TiS3 with strong in-plane anisotropy, and may have relevance to understanding of vibrational properties in other anisotropic two-dimensional material systems.
Transition metal trichalcogenides are layered materials with strong in-plane anisotropy, and their vibrational characteristics remain largely unexplored. Here, the authors present high-pressure Raman studies to uncover unusual vibrational effects within this specific class of materials.
doi:10.1038/ncomms12952
PMCID: PMC5036143  PMID: 27653671
9.  Neuroprotective effect of docosahexaenoic acid nanoemulsion on erectile function in a rat model of bilateral cavernous nerve injury 
Scientific Reports  2016;6:33040.
There is an unmet need for treatment of erectile dysfunction resulting from radical prostatectomy and cavernous nerve (CN) injury. Given the neuroprotective properties of docosahexaenoic acid (DHA), we investigated its effect on penile functional and structural recovery in a rat model of bilateral cavernous nerve injury. Rats were subject to CN injury and received intraperitoneal administration of either vehicle or a DHA nanoemulsion (nano-DHA) at 10, 50, or 250 μg/kg. Functional testing and histological analyses were performed at 28 days post-injury. The maximum intracavernosal pressure (ICP) and other measures of erectile function were significantly higher in the nano-DHA groups than in the vehicle group (p < 0.05). The ratio of area of expression of neuronal nitric oxide synthase (nNOS)/β-III tubulin, numbers of axon and smooth muscle cell content were significantly higher in the 50 μg/kg nano-DHA group than in the vehicle group (p < 0.05). A qualitative increase in the smooth muscle cells/collagen ratio and decrease in apoptosis was observed in the nano-DHA groups relative to the vehicle group: however, these differences were not statistically significant. Our data demonstrate that nano-DHA, particularly the 50 μg/kg regimen, improves erectile function after bilateral CN injury in rats by neuroprotection and other anti-fibrotic and anti-apoptotic mechanisms.
doi:10.1038/srep33040
PMCID: PMC5021993  PMID: 27625175
10.  Microsurgical vasoepididymostomy for patients with infectious obstructive azoospermia: cause, outcome, and associated factors 
Asian Journal of Andrology  2016;18(5):759-762.
Azoospermia is of great importance to male infertility. Obstructive azoospermia (OA) due to infection is the most prevalent form of OA in China and has been less studied. We aim to observe the treatment outcome of microsurgical vasoepididymostomy (VE) and also to identify the factors relative to the result after reconstructive surgery. Two hundred and eight men presenting with OA due to infection during the study period from July 2010 to July 2013 were prospectively evaluated. Clinical examination, semen analysis, serum follicle stimulating hormone (FSH), and scrotal ultrasound were done before surgical exploration. Among the 198 men who were selected for surgical procedures, 159 candidates underwent microsurgical VE with sperm detected in the epididymal fluid. As for the other 39 cases, reconstruction was not feasible. The average age was 28.5 ± 3.9 years (range 22–38), with average follow-up being 16.5 ± 5.9 months (range 4–28). According to the 150 cases being followed after VE procedures, the total patency rate was 72% (108/150). During follow-up, 38.7% (58/150) natural pregnancies occurred, with overall live birth rate being 32.7% (49/150). Our data suggested that microsurgical VE is an effective therapy for postinfectious epididymal OA. Individualized counseling with prognosis based on etiology should be offered to patients to select optical therapy.
doi:10.4103/1008-682X.175095
PMCID: PMC5000800  PMID: 26924282
infection; obstructive azoospermia; vasoepididymostomy
11.  Sulforaphane protects against rotenone-induced neurotoxicity in vivo: Involvement of the mTOR, Nrf2, and autophagy pathways 
Scientific Reports  2016;6:32206.
Sulforaphane, a naturally occurring compound found in cruciferous vegetables, has been shown to be neuroprotective in several neurological disorders. In this study, we sought to investigate the potential protective effects and associated molecular mechanisms of sulforaphane in an in vivo Parkinson’s disease (PD) model, based on rotenone-mediated neurotoxicity. Our results showed that sulforaphane inhibited rotenone-induced locomotor activity deficiency and dopaminergic neuronal loss. Additionally, sulforaphane treatment inhibited the rotenone-induced reactive oxygen species production, malondialdehyde (MDA) accumulation, and resulted in an increased level of total glutathione and reduced glutathione (GSH): oxidized glutathione (GSSG) in the brain. Western blot analysis illustrated that sulforaphane increased the expression of nuclear factor (erythroid-derived 2)-like 2 (Nrf2), heme oxygenase-1 (HO-1), and NAD(P)H quinone oxidoreductase (NQO1), the latter two of which are anti-oxidative enzymes. Moreover, sulforaphane treatment significantly attenuated rotenone-inhibited mTOR-mediated p70S6K and 4E-BP1 signalling pathway, as well as neuronal apoptosis. In addition, sulforaphane rescued rotenone-inhibited autophagy, as detected by LC3-II. Collectively, these findings demonstrated that sulforaphane exert neuroprotective effect involving Nrf2-dependent reductions in oxidative stress, mTOR-dependent inhibition of neuronal apoptosis, and the restoration of normal autophagy. Sulforaphane appears to be a promising compound with neuroprotective properties that may play an important role in preventing PD.
doi:10.1038/srep32206
PMCID: PMC4995453  PMID: 27553905
12.  Cardiac autonomic function in patients with acute exacerbation of chronic obstructive pulmonary disease with and without ventricular tachycardia 
BMC Pulmonary Medicine  2016;16:124.
Background
Autonomic dysfunction in patients with chronic obstructive pulmonary disease (COPD) may increase the risks of arrhythmia and sudden death. We studied cardiac autonomic function in patients with acute exacerbation of COPD (AECOPD).
Methods
Patients with AECOPD were classified into ventricular tachycardia (VT) and non-VT groups according to the presence or absence of VT. The following parameters derived from 24-h Holter monitoring were compared between groups: average heart rate, heart rate deceleration capacity (DC), heart rate acceleration capacity (AC), standard deviation of normal RR intervals (SDNN), standard deviation of average RR interval in 5-min segments (SDANN), root mean square of standard deviations of differences between adjacent normal RR intervals (rMSSD), low-frequency power (LF), high-frequency power (HF) and LF/HF ratio.
Results
Seventy patients were included, 22 in the VT group and 48 in the non-VT group. The groups had similar clinical characteristics (except for more common amiodarone use in the VT group, P < 0.05) and general ECG characteristics. DC, SDNN, SDANN and rMSSD were lower and AC higher in the VT group (P < 0.05). In the VT group, DC was correlated positively with SDNN (r = 0.716), SDANN (r = 0.595), rMSSD (r = 0.571) and HF (r = 0.486), and negatively with LF (r = -0.518) and LF/HF (r = -0.458) (P < 0.05). AC was correlated negatively with SDNN (r = -0.682), SDANN (r = -0.567) and rMSSD (r = -0.548) (P < 0.05).
Conclusions
DC decreased and AC increased in patients with AECOPD and VT, reflecting an imbalance in autonomic regulation of the heart that might increase the risk of sudden death.
doi:10.1186/s12890-016-0287-0
PMCID: PMC4992314  PMID: 27544078
Chronic obstructive pulmonary disease; Acute exacerbation; Electrocardiogram; Autonomic nervous system; Ventricular tachycardia; Phase-rectified signal averaging (PRSA)
13.  Comparison of the accuracy of 99mTc-3P4-RGD2 SPECT and CT in diagnosing solitary pulmonary nodules 
Oncology Letters  2016;12(4):2517-2523.
The aim of the present study was to compare technetium-99m-(polyethylene glycol-4)3-(Arg-Gly-Asp)2 (99mTc-3P4-RGD2) single-photon emission computed tomography (SPECT) and computed tomography (CT) in the noninvasive differentiation of solitary pulmonary nodules (SPNs). The present study prospectively investigated a consecutive series of 24 patients with SPN, who were newly diagnosed using radiography between September 2012 and January 2014. All patients underwent 99mTc-3P4-RGD2 SPECT and CT scans using a dual-head variable-angle γ-camera equipped with high-resolution collimators. A blinded panel of two thoracic radiologists for CT and three nuclear physicians for SPECT analyzed the images using a 5-grade scale. The SPECT images were also semi-quantitatively evaluated using tumor to non-tumor localization ratios (T/NT). The results were verified by pathological examination of the biopsy material obtained from each patient with SPN, and receiver operating characteristic (ROC) curves were generated from these results. The present results revealed that there were 17 malignant and 7 benign SPNs among the 24 patients with SPN. The mean size of the SPN was 2.1±0.6 cm. Sensitivity of visual analysis for SPECT and CT were 100.0 and 82.4%, respectively, and specificity was 71.4% for the two methods. When the T/NT SPECT semiquantitative analysis (ratio, 1.64) was used as a cut-off, the sensitivity and specificity of SPECT were 100.0 and 71.4%, respectively. The areas under the ROC curves were 0.840 for visual analysis of SPECT [95% confidence interval (CI), 0.600–1.000], 0.849 for semiquantitative analysis of SPECT (95% CI, 0.618–1.000) and 0.815 for CT (95% CI, 0.626–1.000). In conclusion, the present results suggest that 99mTc-3P4-RGD2 SPECT is more accurate than CT in the detection of malignant SPN, and visual analysis appears to be sufficient for the characterization of SPN.
doi:10.3892/ol.2016.5030
PMCID: PMC5038481  PMID: 27698821
99mTc-3P4-RGD2; SPECT/CT; solitary pulmonary nodule
14.  Chinese Public Attention to the Outbreak of Ebola in West Africa: Evidence from the Online Big Data Platform 
Objective: The outbreak of the Ebola epidemic in West Africa in 2014 exerted enormous global public reaction via the Internet and social media. This study aimed to investigate and evaluate the public reaction to Ebola in China and identify the primitive correlation between possible influence factors caused by the outbreak of Ebola in West Africa and Chinese public attention via Internet surveillance. Methods: Baidu Index (BDI) and Sina Micro Index (SMI) were collected from their official websites, and the disease-related data were recorded from the websites of the World Health Organization (WHO), U.S. Centers for Disease Control and Prevention (CDC), and U.S. National Ministries of Health. The average BDI of Internet users in different regions were calculated to identify the public reaction to the Ebola outbreak. Spearman’s rank correlation was used to check the relationship of epidemic trends with BDI and SMI. Additionally, spatio-temporal analysis and autocorrelation analysis were performed to detect the clustered areas with the high attention to the topic of “Ebola”. The related news reports were collected from authoritative websites to identify potential patterns. Results: The BDI and the SMI for “Ebola” showed a similar fluctuating trend with a correlation coefficient = 0.9 (p < 0.05). The average BDI in Beijing, Tibet, and Shanghai was higher than other cities. However, the disease-related indicators did not identify potential correlation with both indices above. A hotspot area was detected in Tibet by local autocorrelation analysis. The most likely cluster identified by spatiotemporal cluster analysis was in the northeast regions of China with the relative risk (RR) of 2.26 (p ≤ 0.01) from 30 July to 14 August in 2014. Qualitative analysis indicated that negative news could lead to a continuous increase of the public’s attention until the appearance of a positive news report. Conclusions: Confronted with the risk of cross-border transmission of the infectious disease, online surveillance might be used as an innovative approach to perform public communication and health education through examining the public’s reaction and attitude.
doi:10.3390/ijerph13080780
PMCID: PMC4997466  PMID: 27527196
Ebola; Internet surveillance; public attention; Big Data
15.  The Distribution of Syphilis Among Inpatients in Wenzhou, China: A Hospital Based Study 
Background
The high prevalence of syphilis among inpatients is an important concern in clinical settings. Thus, a better understanding of the serological test would be valuable.
Objectives
We analyzed the serological test results for syphilis among the inpatients in Wenzhou central hospital, China, to estimate the distribution of syphilis this Chinese population.
Patients and Methods
The blood samples of 81946 inpatients at the hospital from January 2010 to December 2012 were collected and retrospectively analyzed. Syphilis testing was conducted using a Treponema pallidum enzyme-linked immunosorbent assay (TP-ELISA) and a TP particle agglutination (TPPA) assay. A toluidine red unheated serum test (TRUST) was then used to determine the titer of TP antibody in the TP- ELISA-positive samples.
Results
In total, 1618 of the 81946 inpatients showed positive syphilis serology; the positive rates in 2010, 2011, and 2012 were 2.27%, 1.58%, and 2.11%, respectively. Males had a significantly higher positive rate when compared to females. Surprisingly, the highest positive rate was observed among patients older than 80 years, followed by patients younger than 19 years, while patients aged 20 - 39 years had the lowest positive rate. The TRUST titer of most TP-positive cases was less than 1:8. Patients aged 20 - 39 years showed the highest percentage of TRUST titer values ≥ 1:8, while patients older than 80 years showed the lowest percentage; the differences between these two groups were statistically significant.
Conclusions
The serological characteristics of syphilis varied with gender and age. Syphilis screening and control should be conducted for young patients and pregnant women, but special attention should also be paid to elderly inpatients. The TRUST assay is better used in syphilis screening and for judgment of curative effects, but the diagnosis needs specific methods, such as the TP-ELISA and the TPPA test.
doi:10.5812/jjm.27825
PMCID: PMC5076385  PMID: 27800128
Syphilis; Inpatient; Serologic Test; Treponema pallidum
16.  The mitochondrial genomes of Culex tritaeniorhynchus and Culex pipiens pallens (Diptera: Culicidae) and comparison analysis with two other Culex species 
Parasites & Vectors  2016;9:406.
Background
Culex tritaeniorhynchus and Culex pipiens pallens are the major vectors of the Japanese encephalitis virus and Wuchereria bancrofti, the causative agent of filariasis. The knowledge of mitochondrial genomes has been widely useful for the studies on molecular evolution, phylogenetics and population genetics.
Methods
In this study, we sequenced and annotated the mitochondrial (mt) genomes of Cx. tritaeniorhynchus and Cx. p. pallens, and performed a comparative analysis including four known mt genomes of species of the subgenus Culex (Culex). The phylogenetic relationships of Cx. tritaeniorhynchus, Cx. p. pallens and four known Culex mt genome sequences were reconstructed by maximum likelihood based on concatenated protein-coding gene sequences.
Results
Culex tritaeniorhynchus and Cx. p. pallens mt genomes are 14,844 bp and 15,617 bp long, both consists of 13 PCGs, 22 tRNAs, 2 rRNAs and 1 CR (not sequenced for Cx. tritaeniorhynchus). The initiation and termination codons of PCGs are ATN and TAA, respectively, except for COI starting with TCG, and COI and COII terminated with T. tRNAs have the typical clover-leaf secondary structures except for trnS(AGN) that is lacking the DHU stem. 16S rRNA and 12S rRNA secondary structures were drawn for the first time for mosquito mt genomes. The control region of Cx. p. pallens mt genome is 747 bp long and with four tandem repeat structures. Phylogenetic analyses demonstrated that the mt genome of Cx. tritaeniorhynchus was significantly separated from the remaining five mt genomes of Culex spp. Culex p. pipiens, Cx. p. pallens and Cx. p. quinquefasciatus formed a monophyletic clade with Cx. p. quinquefasciatus linked in the middle of the clade, and Cx. p. pallens should have the same taxonomic level as Culex p. pipiens and Cx. p. quinquefasciatus.
Conclusions
The mt genomes of Cx. tritaeniorhynchus and Cx. p. pallens share the same gene composition and order with those of two other Culex species. Culex p. pallens of the Pipiens complex should have the same taxonomic level as Culex p. pipiens and Cx. p. quinquefasciatus investigated. We enriched the Culex mt genome data and provided a reference basis for further Culex mt genome sequencing and analyses.
Electronic supplementary material
The online version of this article (doi:10.1186/s13071-016-1694-z) contains supplementary material, which is available to authorized users.
doi:10.1186/s13071-016-1694-z
PMCID: PMC4957372  PMID: 27444629
Culex tritaeniorhynchus; Culex pipiens pallens; Culex; Mitochondrial genome; Characteristics; Phylogenetics
17.  Tyrosine Hydroxylase is crucial for maintaining pupal tanning and immunity in Anopheles sinensis 
Scientific Reports  2016;6:29835.
Tyrosine hydroxylase (TH), the initial enzyme in the melanin pathway, catalyzes tyrosine conversion into Dopa. Although expression and regulation of TH have been shown to affect cuticle pigmentation in insects, no direct functional studies to date have focused on the specific physiological processes involving the enzyme during mosquito development. In the current study, silencing of AsTH during the time period of continuous high expression in Anopheles sinensis pupae led to significant impairment of cuticle tanning and thickness, imposing a severe obstacle to eclosion in adults. Meanwhile, deficiency of melanin in interference individuals led to suppression of melanization, compared to control individuals. Consequently, the ability to defend exogenous microorganisms declined sharply. Accompanying down-regulation of the basal expression of five antimicrobial peptide genes resulted in further significant weakening of immunity. TH homologs as well as the composition of upstream transcription factor binding sites at the pupal stage are highly conserved in the Anopheles genus, implying that the TH-mediated functions are crucial in Anopheles. The collective evidence strongly suggests that TH is essential for Anopheles pupae tanning and immunity and provides a reference for further studies to validate the utility of the key genes involved in the melanization pathway in controlling mosquito development.
doi:10.1038/srep29835
PMCID: PMC4945905  PMID: 27416870
18.  Secondary coordination sphere accelerates hole transfer for enhanced hydrogen photogeneration from [FeFe]-hydrogenase mimic and CdSe QDs in water 
Scientific Reports  2016;6:29851.
Achieving highly efficient hydrogen (H2) evolution via artificial photosynthesis is a great ambition pursued by scientists in recent decades because H2 has high specific enthalpy of combustion and benign combustion product. [FeFe]-Hydrogenase ([FeFe]-H2ase) mimics have been demonstrated to be promising catalysts for H2 photoproduction. However, the efficient photocatalytic H2 generation system, consisting of PAA-g-Fe2S2, CdSe QDs and H2A, suffered from low stability, probably due to the hole accumulation induced photooxidation of CdSe QDs and the subsequent crash of [FeFe]-H2ase mimics. In this work, we take advantage of supramolecular interaction for the first time to construct the secondary coordination sphere of electron donors (HA−) to CdSe QDs. The generated secondary coordination sphere helps realize much faster hole removal with a ~30-fold increase, thus leading to higher stability and activity for H2 evolution. The unique photocatalytic H2 evolution system features a great increase of turnover number to 83600, which is the highest one obtained so far for photocatalytic H2 production by using [FeFe]-H2ase mimics as catalysts.
doi:10.1038/srep29851
PMCID: PMC4945928  PMID: 27417065
19.  A DNA Binding Protein Is Required for Viral Replication and Transcription in Bombyx mori Nucleopolyhedrovirus 
PLoS ONE  2016;11(7):e0159149.
A DNA-binding protein (DBP) [GenBank accession number: M63416] of Bombyx mori nuclear polyhedrosis virus (BmNPV) has been reported to be a regulatory factor in BmNPV, but its detailed functions remain unknown. In order to study the regulatory mechanism of DBP on viral proliferation, genome replication, and gene transcription, a BmNPV dbp gene knockout virus dbp-ko-Bacmid was generated by the means of Red recombination system. In addition, dbp-repaired virus dbp-re-Bacmid was constructed by the means of the Bac to Bac system. Then, the Bacmids were transfected into BmN cells. The results of this viral titer experiment revealed that the TCID50 of the dbp-ko-Bacmid was 0; however, the dbp-re-Bacmid was similar to the wtBacmid (p>0.05), indicating that the dbp-deficient would lead to failure in the assembly of virus particles. In the next step, Real-Time PCR was used to analyze the transcriptional phases of dbp gene in BmN cells, which had been infected with BmNPV. The results of the latter experiment revealed that the transcript of dbp gene was first detected at 3 h post-infection. Furthermore, the replication level of virus genome and the transcriptional level of virus early, late, and very late genes in BmN cells, which had been transfected with 3 kinds of Bacmids, were analyzed by Real-Time PCR. The demonstrating that the replication level of genome was lower than that of wtBacmid and dbp-re-Bacmid (p<0.01). The transcriptional level of dbp-ko-Bacmid early gene lef-3, ie-1, dnapol, late gene vp39 and very late gene p10 were statistically significantly lower than dbp-re-Bacmid and wtBacmid (p<0.01). The results presented are based on Western blot analysis, which indicated that the lack of dbp gene would lead to low expressions of lef3, vp39, and p10. In conclusion, dbp was not only essential for early viral replication, but also a viral gene that has a significant impact on transcription and expression during all periods of baculovirus life cycle.
doi:10.1371/journal.pone.0159149
PMCID: PMC4945074  PMID: 27414795
20.  Who Is Vulnerable to Dengue Fever? A Community Survey of the 2014 Outbreak in Guangzhou, China 
Unprecedented dengue fever (DF) outbreaks impel China to develop useful disease control strategies. Integrated vector management (IVM) focuses on identifying vulnerable populations and interrupting human–vector contact; however, vulnerable populations have not been clearly identified in China. We conducted a case-control study during the initial stage of the 2014 DF outbreak in Guangzhou, China to assess risk factors for DF infection. Cases were randomly sampled from the National Notifiable Infectious Disease Reporting Information System (NNIDRIS). Controls were healthy individuals recruited from 17 DF infected communities through cluster sampling. A structured questionnaire on demographics, knowledge, practices, and living environment was administered to participants (165 cases; 492 controls). Logistic regression models identified characteristics of vulnerable populations. Awareness of dengue (OR = 0.08, 95% CI = 0.04–0.17), removing trash and stagnant water from around the residence (OR = 0.02, 95% CI = 0.00–0.17), and using mosquito repellent oils (OR = 0.36, 95% CI = 0.16–0.81) were protective factors. Living in an old flat or shed (OR = 2.38, 95% CI = 1.18–4.79) was a risk factor. Coils and bed nets were not protective due to incorrect knowledge of use. Using mosquito repellent oils and other protective measures can reduce vulnerability to DF infection.
doi:10.3390/ijerph13070712
PMCID: PMC4962253  PMID: 27428986
dengue fever; knowledge; lifestyle; risk factors; vector control
21.  Metformin Alleviated Aβ-Induced Apoptosis via the Suppression of JNK MAPK Signaling Pathway in Cultured Hippocampal Neurons 
BioMed Research International  2016;2016:1421430.
Both diabetes and hyperinsulinemia are confirmed risk factors for Alzheimer's disease. Some researchers proposed that antidiabetic drugs may be used as disease-modifying therapies, such as metformin and thiazolidinediones, although more evidence was poorly supported. The aim of the current study is to investigate the role of metformin in Aβ-induced cytotoxicity and explore the underlying mechanisms. First, the experimental results show that metformin salvaged the neurons exposed to Aβ in a concentration-dependent manner with MTT and LDH assay. Further, the phosphorylation levels of JNK, ERK1/2, and p38 MAPK were measured with western blot analysis. It was investigated that Aβ increased phospho-JNK significantly but had no effect on phospho-p38 MAPK and phospho-ERK1/2. Metformin decreased hyperphosphorylated JNK induced by Aβ; however, the protection of metformin against Aβ was blocked when anisomycin, the activator of JNK, was added to the medium, indicating that metformin performed its protection against Aβ in a JNK-dependent way. In addition, it was observed that metformin protected the neurons via the suppression of apoptosis. Taken together, our findings demonstrate that metformin may have a positive effect on Aβ-induced cytotoxicity, which provides a preclinical strategy against AD for elders with diabetes.
doi:10.1155/2016/1421430
PMCID: PMC4925968  PMID: 27403417
22.  Social support received by multidrug-resistant tuberculosis patients and related factors: a cross-sectional study in Zhejiang Province, People’s Republic of China 
Patient preference and adherence  2016;10:1063-1070.
Objectives
The objective of this study is to assess the social support received by patients diagnosed with multidrug-resistant tuberculosis (MDR-TB) in Zhejiang Province, People’s Republic of China and the factors that may have influenced it.
Methods
A total of 220 MDR-TB patients participated in the questionnaire-based survey, and the data from 212 valid questionnaires were analyzed. The respondents reported their sociodemographic status, disease features, and attitudes toward the disease. The social support rating scale was used to measure the patients’ social support scores. An Independent Samples t-test, one-way analysis of variance, and a multiple linear regression model were used to analyze the related factors for the social support scores.
Result
The average social support score of each MDR-TB patient was 32.56±7.86. Participants who were single, widowed or divorced, retired, and had fewer family members and lower family income were found to have lower social support scores. Participants unwilling to disclose their disease tended to have less social support (31.59<34.23, P=0.010). Participants who perceived great help from health care workers reported higher social support rating scale scores than those who perceived no help (35.36.29.89, P=0.014).
Conclusion
MDR-TB patients in Zhejiang Province were shown to have a low level of social support. Patients who were not married, had smaller families, and lower family income received less social support, suggesting that family harmony could be an important source of social support. Patients’ self-isolation may contribute to a decrease in the amount of support they receive from their surroundings. Health care organizations need to offer more social support to MDR-TB patients.
doi:10.2147/PPA.S105655
PMCID: PMC4912324  PMID: 27358557
multidrug-resistant TB; social support; factors
23.  Electroacupuncture improves cognitive ability following cerebral ischemia reperfusion injury via CaM-CaMKIV-CREB signaling in the rat hippocampus 
The aim of the present study was to investigate the effect of electroacupuncture (EA) on cognitive deficits, and the underlying mechanism following cerebral ischemia-reperfusion (I/R) via the calmodulin (CaM)-calmodulin-dependent protein kinase type IV (CaMKIV)-cyclic adenosine monophosphate response elements binding protein (CREB) intracellular signaling pathway in the hippocampus. In total, 45 adult female Sprague-Dawley rats were randomly divided into three groups, namely the sham group, the middle cerebral artery occlusion (MCAO) group and the MCAO + EA group. Rats in the MCAO and MCAO + EA groups were modeled for post-stroke cognitive impairment. EA was performed at the Baihui and Shenting acupuncture points for 30 min/day for one week in the MCAO + EA group. Behavioral testing was analyzed using a step-down apparatus, while 2,3,5-triphenyl tetrazolium chloride was used to detect the infarct volume and lesion size. In addition, CaM activity was assessed by cyclic nucleotide-dependent phosphodiesterase analysis, and the protein expression levels of CaM, CaMKIV, phosphorylated (p)-CaMKIV, CREB and p-CREB were analyzed by western blot analysis. The cerebral I/R injured rat model in the MCAO group was established successfully with regard to the infarct volume and neuronal lesion size, as compared with the sham group. EA was demonstrated to effectively improve the cognitive ability, as measured by the step-down apparatus test, and decrease the infarct volume when compared with the MCAO group (P<0.05). The step-down apparatus test for the EA-treated rats revealed improved learning and reduced memory impairment when compared with the MCAO group. Furthermore, CaM activity and CaM protein expression levels in the MCAO + EA group were lower compared with those in the MCAO group (P<0.05). By contrast, the protein expression levels of CaMKIV, p-CaMKIV, CREB and p-CREB were significantly reduced in the MCAO group when compared with the sham group (P<0.05), although the expression levels increased following EA treatment when compared with the MCAO group (P<0.05). Therefore, cognitive repair benefited from EA, and the main intracellular signaling pathway in the hippocampus was mediated by CaM-CaMKIV-CREB. EA effectively inhibited the expression and activity of CaM, while further enhancing the expression of CaMKIV and CREB, and their associated phosphorylated functions.
doi:10.3892/etm.2016.3428
PMCID: PMC4950700  PMID: 27446275
electroacupuncture; cognitive deficits; cerebral ischemia-reperfusion; calmodulin; calmodulin-dependent protein kinase type IV; cyclic adenosine monophosphate response elements binding protein; hippocampus
24.  A taxonomic account of the genus Stenodynerus from China, with descriptions of five new species (Hymenoptera, Vespidae, Eumeninae) 
ZooKeys  2016;17-48.
In this paper, 20 species of the genus Stenodynerus are reviewed and identified from China, including five new species: Stenodynerus ninglangensis Ma & Li, sp. n., Stenodynerus reflexus Ma & Li, sp. n., Stenodynerus similibaronii Ma & Li, sp. n., Stenodynerus strigatus Ma & Li, sp. n., and Stenodynerus tenuilamellatus Ma & Li, sp. n., and five new records: Stenodynerus baronii Giordani Soika, Stenodynerus bluethgeni van der Vecht, Stenodynerus picticrus (Thomson), Stenodynerus pullus Gusenleitner and Stenodynerus nepalensis Giordani Soika. The five new species are described and illustrated in detail. Moreover, the diagnostic characters of all new records and known species from China are provided, with a key to the Chinese species of Stenodynerus.
doi:10.3897/zookeys.595.7734
PMCID: PMC4926689  PMID: 27408566
Hymenoptera; Vespidae; Eumeninae; Stenodynerus; new species; China; distribution
25.  A Bibliometric Analysis of PubMed Literature on Middle East Respiratory Syndrome 
Middle East Respiratory Syndrome (MERS), a pandemic threat to human beings, has aroused huge concern worldwide, but no bibliometric studies have been conducted on MERS research. The aim of this study was to map research productivity on the disease based on the articles indexed in PubMed. The articles related to MERS dated from 2012 to 2015 were retrieved from PubMed. The articles were classified into three categories according to their focus. Publication outputs were assessed and frequently used terms were mapped using the VOS viewer software. A total of 443 articles were included for analysis. They were published in 162 journals, with Journal of Virology being the most productive (44 articles; 9.9%) and by six types of organizations, with universities being the most productive (276 articles; 62.4%).The largest proportion of the articles focused on basic medical sciences and clinical studies (47.2%) and those on prevention and control ranked third (26.2%), with those on other focuses coming in between (26.6%). The articles on prevention and control had the highest mean rank for impact factor (IF) (226.34), followed by those on basic medical sciences and clinical studies (180.23) and those on other focuses (168.03). The mean rank differences were statistically significant (p = 0.000). Besides, “conronavirus”, “case”, “transmission” and “detection” were found to be the most frequently used terms. The findings of this first bibliometric study on MERS suggest that the prevention and control of the disease has become a big concern and related research should be strengthened.
doi:10.3390/ijerph13060583
PMCID: PMC4924040  PMID: 27304963
Middle East Respiratory Syndrome; MERS; literature review; bibliometrics

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