[Research progress on the role of respiratory microbiome in ventilator-associated pneumonia].

Respiratory microbiome is extensively involved in human life activities and affects lung health and disease states through metabolism and immune regulation. Based on 16S rRNA gene sequencing and other methods, it is obvious that the diversity and the changes in the structure of respiratory microbiome and the dominant proliferation of pathogens are strongly related to the occurrence, development and clinical prognosis of ventilator-associated pneumonia (VAP). The mechanism by which respiratory microbiota promotes the clearance of pathogens may include the following aspects: (1) pre-stimulating innate immune system to increase the number of immune effector cells; (2) regulating pattern recognition receptor (PRR) to moderately promote the production of cytokines; (3) inducing the differentiation of neutrophils into specific subtypes and increasing the expression of antimicrobial genes; (4) producing free fatty acids and organic compounds that are capable of positively modulating the immune system. In conclusion, intervention of microbiome is beneficial to VAP patients. Therefore, this review illustrates the changes of respiratory flora in VAP and its effect on host immunity. At the same time, based on the review of the adjuvant treatment of VAP with probiotics, we put forward the prospect of respiratory commensal bacteria as a new clinical probiotic, in order to deepen the clinical understanding of the role of respiratory flora in VAP, and then provide new ideas for the evaluation of treatment and prognosis.

Phenylalanine promotes alveolar macrophage pyroptosis via the activation of CaSR in ARDS.

Acute respiratory distress syndrome (ARDS) is associated with high mortality rates in patients admitted to the intensive care unit (ICU) patients with overwhelming inflammation considered to be an internal cause. The authors' previous study indicated a potential correlation between phenylalanine levels and lung injury. Phenylalanine induces inflammation by enhancing the innate immune response and the release of pro-inflammatory cytokines. Alveolar macrophages (AMs) can respond to stimuli via synthesis and release of inflammatory mediators through pyroptosis, one form of programmed cell death acting through the nucleotide-binging oligomerization domain-like receptors protein 3 (NLRP3) signaling pathway, resulting in the cleavage of caspase-1 and gasdermin D (GSDMD) and the release of interleukin (IL) -1ß and IL-18, aggravating lung inflammation and injury in ARDS. In this study, phenylalanine promoted pyroptosis of AMs, which exacerbated lung inflammation and ARDS lethality in mice. Furthermore, phenylalanine initiated the NLRP3 pathway by activating the calcium-sensing receptor (CaSR). These findings uncovered a critical mechanism of action of phenylalanine in the context of ARDS and may be a new treatment target for ARDS.

Development and Validation of a Nomogram for Predicting the Risk of Coronavirus-Associated Acute Respiratory Distress Syndrome: A Retrospective Cohort Study.

Background: Since the outbreak of coronavirus disease (COVID-19) in December 2019 in Wuhan, it has spread rapidly worldwide. We aimed to establish and validate a nomogram that predicts the probability of coronavirus-associated acute respiratory distress syndrome (CARDS). Methods: In this single-centre, retrospective study, 261 patients with COVID-19 were recruited using positive reverse transcription-polymerase chain reaction tests for severe acute respiratory syndrome coronavirus 2 in Tongji Hospital at Huazhong University of Science and Technology (Wuhan, China). These patients were randomly distributed into the training cohort (75%) and the validation cohort (25%). The factors included in the nomogram were determined using univariate and multivariate logistic regression analyses based on the training cohort. The area under the receiver operating characteristic curve (AUC), consistency index (C-index), calibration curve, and decision curve analysis (DCA) were used to evaluate the efficiency of the nomogram in the training and validation cohorts. Results: Independent predictive factors, including fasting plasma glucose, platelet, D-dimer, and cTnI, were determined using the nomogram. In the training cohort, the AUC and concordance index were 0.93. Similarly, in the validation cohort, the nomogram still showed great distinction (AUC: 0.92) and better calibration. The calibration plot also showed a high degree of agreement between the predicted and actual probabilities of CARDS. In addition, the DCA proved that the nomogram was clinically beneficial. Conclusion: Based on the results of laboratory tests, we established a predictive model for acute respiratory distress syndrome in patients with COVID-19. This model shows good performance and can be used clinically to identify CARDS early. Trial Registration: Ethics committee of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine (No.:(2020) Linlun-34th).

A Systematic Review and Meta-Analysis of Seasonal Influenza Vaccination of Health Workers.

A systematic review and meta-analysis was conducted to estimate the pooled effect of influenza vaccinations for health workers (HWs). Nine databases were screened to identify randomized clinical trials and comparative observational studies that reported the effect of influenza vaccination among HWs. The risk ratio (RR), standardized mean difference, and 95% confidence interval (CI) were employed to study the effect size using fixed/random-effect models. Subgroup analyses and sensitivity analyses were conducted accordingly. Publication bias was examined. Sixteen studies (involving 7971 HWs from nine countries) were included after a comprehensive literature search. The combined RR regarding the incidence of laboratory-confirmed influenza was 0.36 (95% CI: 0.25 to 0.54), the incidence of influenza-like illness (ILI) was 0.69 (95% CI: 0.45 to 1.06), the absenteeism rate was 0.63 (95% CI: 0.46 to 0.86), and the integrated standardized mean difference of workdays lost was -0.18 (95% CI: -0.28 to -0.07) days/person. The subgroup analysis indicated that vaccination significantly decreases the incidence of laboratory-confirmed influenza in different countries, study populations, and average-age vaccinated groups. Influenza vaccinations could effectively reduce the incidence of laboratory-confirmed influenza, absenteeism rates, and workdays lost among HWs. It is advisable, therefore, to improve the coverage and increase the influenza vaccination count among HWs, which may benefit both workers and medical institutions.

Association of Increased Circulating Acetic Acid With Poor Survival in Pseudomonas aeruginosa Ventilator-Associated Pneumonia Patients.

Background: We previously found that microbial disruption in Pseudomonas aeruginosa ventilator-associated pneumonia (PA-VAP) patients are long-lasting. Long-term microbial dysbiosis may lead to changes in metabolites. Short-chain fatty acids (SCFAs) are microbial fermentation products and show beneficial effects in patients with pneumonia. In this study, we aimed to explore the association between circulating SCFA levels and clinical outcomes in patients with PA-VAP. Methods: In this study, we analyzed SCFAs in the serum of 49 patients with PA-VAP by gas chromatography-mass spectrometry analysis. Twenty of these patients died, and 29 survived. The correlation between serum SCFAs and patient survival and immune parameters was analyzed. Results: We developed a partial least squares discriminant analysis (PLS-DA) model to examine differential SCFAs in 49 patients with PA-VAP. Among the seven SCFAs, only acetic acid was increased in non-survivors (P = 0.031, VIP > 1). Furthermore, high levels of acetic acid (>1.96ug/ml) showed increased 90-day mortality compared to low levels of acetic acid (<1.96ug/ml) in Kaplan-Meier survival analyses (P = 0.027). Increased acetic acid also correlated with reduced circulating lymphocyte and monocyte counts. Conclusion: Our study showed that increased circulating acetic acid is associated with 90-day mortality in PA-VAP patients. The decrease in lymphocytes and monocytes might be affected by acetic acid and involved in the poor prognosis.

The impact of emission trading schemes on firm competitiveness: Evidence of the mediating effects of firm behaviors from the guangdong ETS.

The pilot carbon emission trading scheme in Guangdong Province (GD ETS) of China has fulfilled seven compliance periods, and its potential impact on regulated firms has drawn increasing attention. This article empirically investigated the impact of the ETS on firm behaviors and competitiveness (i.e., cost competitiveness and green competitiveness) by surveying all power firms in the GD ETS. Low-carbon management, carbon asset transactions, and energy saving and emission reduction technology were identified as firm behaviors. The relationships among the ETS, firm behaviors, and firm competitiveness were tested by using bootstrap multiple mediation analyses. The results showed that the GD ETS has a positive impact on firm behaviors. The three examined firm behaviors actually reflect the depth of firm participation in the ETS. The more the firm participates, the greater the mediating effects that the firm behaviors exert on firm competitiveness are. Both carbon asset transactions and energy saving and emission reduction technology have a mediating effect on the relationship between the GD ETS and cost competitiveness, while only the latter mediates the relationship between the GD ETS and green competitiveness. Implications for policy makers and firm operators were discussed.

Single-layer multitasking vortex-metalens for ultra-compact two-photon excitation STED endomicroscopy imaging.

With the novel capabilities of engineering the optical wavefront at the nanoscale, the dielectric metalens has been utilized for fluorescence microscopy imaging system. However, the main technical difficulty is how to realize the achromatic focusing and light modulation simultaneously by a single-layer metalens in the two-photon excitation STED (TPE-STED) endomicroscopy imaging system. Herein, by combining the spatial multiplexing technology and vortex phase modulation, a single-layer multitasking vortex-metalens as a miniature microscopy objective on the end of fiber was proposed. The multitasking vortex-metalens with 36-sectors interleaving (diameter of 100 µm) could focus the excitation beam (1050 nm) and depletion beam (599 nm) to the same focal distance, modulate a doughnut-shaped depletion spot with vortex phase and reshape the focal spots to further make improvement in the quality and symmetry. According to the TPE-STED theory, a symmetrical effective fluorescent spot with the lateral resolution of 30 nm was obtained by the proposed metalens. Thus, with the advantage of ultra-compact and lightweight, we prospect that the subminiature multitasking metalens will help guide future developments in high-performance metalenses toward high-resolution and real-time images for deep biological tissue in vivo and enable scientific high-end miniature endomicroscopy imaging system.

NaYF4:Yb/Tm@SiO2-Dox/Cur-CS/OSA nanoparticles with pH and photon responses.

Stimulus-triggered drug delivery systems (DDSs) based on lanthanide-doped upconversion nanoparticles (UCNPs) have attracted significant attention for treating cancers due to their merits of high drug availability, precisely controlled drug release, and low side-effects. However, such DDSs usually exhibit a single stimulus-response, which may limit the efficiency of cancer treatment. To extend response types in a single DDS, we construct NaYF4:Yb/Tm@SiO2-doxorubicin (Dox)/curcumin (Cur)-chitosan (CS)/2-Octen-1-ylsuccinic anhydride (OSA) nanoparticles with core-shell structures. Our method is based on the exploration of the synergistic effect of UCNPs and multiple drugs. In particular, the NaYF4:Yb/Tm is used to convert near-infrared light to visible light, activating Cur photosensitizers to produce singlet oxygen for photodynamic therapy, while CS/OSA responds to a low pH environment to release cancer drugs, including Dox and Cur for chemotherapy through breaking a free carboxyl group. The results show that the UCNPs with a 40 nm diameter, 23 nm thick mesoporous SiO2, and 19/1 mol% Yb3+/Tm3+concentrations could continuously release Dox and Cur at a pH value of 6.5 within 6 h after the excitation of a 980 nm-wavelength CW laser. Our study provides a promising approach for developing efficient DDSs for cancer treatment.

Soluble PD-L1 improved direct ARDS by reducing monocyte-derived macrophages.

Acute respiratory distress syndrome (ARDS) is common in intensive care units (ICUs), although it is associated with high mortality, no effective pharmacological treatments are currently available. Despite being poorly understood, the role of programmed cell death protein 1 (PD-1) and PD-ligand 1 (PD-L1) axis in ARDS may provide significant insights into the immunosuppressive mechanisms that occur after ARDS. In the present study, we observed that the level of soluble PD-L1 (sPD-L1), a potential activator of the PD-1 pathway, was upregulated in survivors of direct ARDS than in non-survivors. Administration of sPD-L1 in mice with direct ARDS relieved inflammatory lung injury and improved the survival rate, indicating the protective role of sPD-L1 in direct ARDS. Using high-throughput mass cytometry, we found a marked decrease in the number of lung monocyte-derived macrophages (MDMs) with proinflammatory markers, and the protective role of sPD-L1 diminished in ARDS mice with monocyte/macrophage depletion. Furthermore, PD-1 expression increased in the MDMs of patients and mice with direct ARDS. Finally, we showed that sPD-L1 induced MDM apoptosis in patients with direct ARDS. Taken together, our results demonstrated that the engagement of sPD-L1 on PD-1 expressing macrophages resulted in a decrease in pro-inflammatory macrophages and eventually improved direct ARDS. Our study identified a prognostic indicator for patients with direct ARDS and a potential target for therapeutic development in direct ARDS.

Excitation and emission dual-wavelength confocal metalens designed directly in the biological tissue environment for two-photon micro-endoscopy.

With the advantages of completely controlling the phase, amplitude, and polarization in subwavelength range, metalenses have drawn intensive attentions in high resolution two-photon micro-endoscopic fluorescence imaging system. However, chromatic dispersion and severe scattering of biological tissue significantly reduce excitation-collection efficiency in the traditional two-photon imaging system based on traditional metalenses designed in the air background. Here, an excitation and emission dual-wavelength confocal and polarization-insensitive metalens designed in the biological tissue environment was proposed by adopting the composite embedding structure and spatial multiplexing approach. The metalens with numerical aperture (NA) of 0.895 can focus the excitation (915 nm) and emission (510 nm) beams to the same focal spot in the mouse cortex. According to the theoretical simulation of two-photon fluorescence imaging, the lateral resolution of the collected fluorescent spots via the proposed metalens can be up to 0.42 µm. Compared to the metalens designed in the air environment, the collection efficiency of fluorescent spot is improved from 5.92% to 14.60%. Our investigation has opened a new window of high resolution and minimally invasive imaging in deep regions of biological tissues.

Increased mortality of acute respiratory distress syndrome was associated with high levels of plasma phenylalanine.

BACKGROUND: There is a dearth of drug therapies available for the treatment of acute respiratory distress syndrome (ARDS). Certain metabolites play a key role in ARDS and could serve as potential targets for developing therapies against this respiratory disorder. The present study was designed to determine such "functional metabolites" in ARDS using metabolomics and in vivo experiments in a mouse model. METHODS: Metabolomic profiles of blood plasma from 42 ARDS patients and 28 healthy controls were captured using Ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) assay. Univariate and multivariate statistical analysis were performed on metabolomic profiles from blood plasma of ARDS patients and healthy controls to screen for "functional metabolites", which were determined by variable importance in projection (VIP) scores and P value. Pathway analysis of all the metabolites was performed. The mouse model of ARDS was established to investigate the role of "functional metabolites" in the lung injury and mortality caused by the respiratory disorder. RESULTS: The metabolomic profiles of patients with ARDS were significantly different from healthy controls, difference was also observed between metabolomic profiles of the non-survivors and the survivors among the ARDS patient pool. Levels of Phenylalanine, D-Phenylalanine and Phenylacetylglutamine were significantly increased in non-survivors compared to the survivors of ARDS. Phenylalanine metabolism was the most notably altered pathway between the non-survivors and survivors of ARDS patients. In vivo animal experiments demonstrated that high levels of Phenylalanine might be associated with the severer lung injury and increased mortality of ARDS. CONCLUSION: Increased mortality of acute respiratory distress syndrome was associated with high levels of plasma Phenylalanine. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1800015930. Registered 29 April 2018, http://www.chictr.org.cn/edit.aspx?pid=25609&htm=4.

Enhanced Thermoelectric Properties of Ca3-xAgxCo4O9 by the Sol⁻Gel Method with Spontaneous Combustion and Cold Isostatic Pressing.

In this study, Ca3-xAgxCo4O9 ceramics were synthesized by the sol⁻gel method combined with spontaneous combustion and cold isostatic pressing. The Ca3-xAgxCo4O9 ceramics were characterized via X-ray diffraction and scanning electron microscopy. Thermoelectric properties of the ceramics were measured from 323 to 673 K. The results indicated that Ag doping significantly affected the microstructure and thermoelectric properties. With the increase in Ag content and gradual increase in electrical conductivity, the Seebeck coefficient first increased and then decreased, whereas the thermal conductivity exhibited the opposite case. The figure of merit, ZT, was 0.17 at 673 K for the Ca2.8Ag0.2Co4O9 sample. These results indicated that the thermoelectric properties could be optimized remarkably with the substitution of Ag.

Lower respiratory tract microbial composition was diversified in Pseudomonas aeruginosa ventilator-associated pneumonia patients.

BACKGROUND: Probiotics could prevent Pseudomonas aeruginosa colonization in lower respiratory tract (LRT) and reduced P. aeruginosa ventilator-associated pneumonia (VAP) rate. Recent studies also suggested that probiotics could improve lung inflammation in mice infected with P. aeruginosa. It seems that microbiota regulation may be a potential therapy for P. aeruginosa VAP patients. However, we know less about the LRT microbial composition and its correlation with prognosis in P. aeruginosa VAP patients. This study aimed to characterize LRT microbiota in P. aeruginosa VAP patients and explore the relationship between microbiota and patient prognosis. METHODS: Deep endotracheal secretions were sampled from subjects via intubation. Communities were identified by 16S ribosomal RNA gene sequencing. The relationship between microbiota and the prognosis of P. aeruginosa VAP patients were evaluated. Clinical pulmonary infection score and the survival of intensive care unit were both the indicators of patient prognosis. RESULTS: In this study, the LRT microbial composition of P. aeruginosa VAP patients was significantly different from non-infected intubation patients, and showed significant individual differences, forming two clusters. According to the predominant phylum of each cluster, these two clusters were named Pro cluster and Fir-Bac cluster respectively. Patients from Pro cluster were dominated by Proteobacteria (adj.P < 0.001), while those from Fir-Bac cluster were dominated by Firmicutes, and Bacteroidetes (both adj.P < 0.001). These two varied clusters (Pro and Fir-Bac cluster) were associated with the patients' primary disease (χ2-test, P < 0.0001). The primary disease of the Pro cluster mainly included gastrointestinal disease (63%), and the Fir-Bac cluster was predominantly respiratory disease (89%). During the two-week dynamic observation period, despite the use of antibiotics, the dominant genera and Shannon diversity of the LRT microbiota did not change significantly in patients with P. aeruginosa VAP. In prognostic analysis, we found a significant negative correlation between Lactobacillus and clinical pulmonary infection score on the day of diagnosis (P = 0.014); but we found no significant difference of microbial composition between survivors and non-survivors. CONCLUSIONS: LRT microbial composition was diversified among P. aeruginosa VAP patients, forming two clusters which were associated with the primary diseases of the patients.

Tet1-mediated DNA demethylation involves in neuron damage induced by bilirubin in vitro.

The aim of this study is to identify the role of Tet1-mediated DNA demethylation in the neurotoxicity caused by unconjugated bilirubin (UCB) in vitro. Primary neuronal cells after cultured for 72 h were exposed to UCB (0-100 µmol/L) for 24 h. Following exposure to UCB cytotoxicity was determined with the methyl tetrazolium (MTT) assay, reactive oxygen species (ROS) and caspase-3 activity in neuron cells were measured with the corresponding assay kits. The expression of Tet1 and Klotho was determined with RT-PCR at mRNA level and western blot at protein level. Our results showed that UCB can cause time-dependent and dose-dependent reduction of cell viability of neuronal cells, induce oxidative stress through increasing the production of ROS and increase caspase-3 activity. Quantitative real-time PCR and western blot analysis showed that UCB can inhibit Tet1 and Klotho expression in cultured neuronal cells at both the mRNA and protein level, respectively. These results are first to suggest UCB may, in part, exert its neurotoxicity through alteration of the neuronal antioxidant status and inhibition of Klotho and Tet1 gene expression. The elevation of DNA methylation in global genome through inhibition of Tet1 gene expression may, in part, play an important role in the neurotoxicity caused by UCB in vitro.

[Effects of Porphyromnonas gingivalis lipopolysaccharide on the expression of RANTES and fractalkine in human urnbilical vein endothelial cells].

OBJECTIVE: A study was conducted to investigate the effects of Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) on the expression of regulated upon activation normal T-cell expressed and secreted (RANTES) and fractalkine in human umbilical vein endothelial cells (HUVECs). METHODS: HUVECs were incubated with different concentrations of Pg-LPS (200, 500, and 1000 ng x mL(-1)) for 1, 6, 12, and 24 h, respectively. Then real time quantitative polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent method (ELISA) were adopted to detect the protein levels and mRNA levels of RANTES and fractalkine. RESULTS: The RANTES protein levels and mRNA levels, as well as fractalkine mRNA levels, were significantly higher in all experimental groups of 1, 6, and 12 h than in the control group (P<0.05), except the expression of RANTES mRNA in 200 ng x mL(-1) group of 12 h and RANTES protein in 200 ng x mL(-1) group of 1 h. The expression levels of RANTES mRNA and fractalkine mRNA were highest in 1000 ng x mL(-1) group of 6 h and were 4.88- and 6.20-fold higher, respectively, than those in the control group. The expression levels of RANTES protein, mRNA, and fractalkine mRNA decreased 6 h after stimulation, and were significantly higher than those in the control group (P<0.05) in the RANTES and fractalkine in HUVEC, and such expression is important in the development of atherosclerosis 500 ng x mL(-1) group of 24 h. There was a significant difference between the expression of fractalkine mRNA in 1000 ng x mL(-1) group of 6 and 12 h than in the control group (P<0.05). CONCLUSION: Pg-LPS infection might up-regulate the expression of RANTES and fractalkine in HUVEC, and such expression is important in the development of atherosclerosis.

Conductive polypyrrole/viscose fiber composites.

Polypyrrole (PPy) was polymerized with pyrrole (Py) as the monomer, FeCl3 as an oxidant and sodium dodecyl benzene sulfonate (SDBS) as the dopant on the surface of viscose fiber (VCF) to prepare the conductive PPy/VCF composites. Fourier transform infrared spectra (FT-IR), thermal gravimetric analysis (TGA) and X-ray photoelectron spectroscope (XPS) proved that the interaction between PPy and VCF formed in the PPy/VCF composites. Three structures of N atoms (imine, amine and cationic atoms) were found in PPy of PPy/VCF composites. The influence of reaction conditions including reaction time, Py concentration, FeCl3 concentration and SDBS concentration on the morphology and the conductivity of PPy/VCF composites was investigated in detail. The orthogonal experiments were designed to determine the optimal reaction conditions: reaction time 5h, Py concentration 0.1 mol/L and FeCl3 concentration 0.25 mol/L. When PPy/VCF composite was washed 50 times in water, the conductivity still kept at 1.5S/cm, and this value was stable for more washing.

Effectiveness of peer support for improving glycaemic control in patients with type 2 diabetes: a meta-analysis of randomized controlled trials.

BACKGROUND: To assess the effects of peer support at improving glycemic control in patients with type 2 diabetes. METHODS: Relevant electronic databases were sought for this investigation up to Dec 2014. Randomized controlled trials involving patients with type 2 diabetes that evaluated the effect of peer support on glycated hemoglobin (HbA1c) concentrations were included. The pooled mean differences (MD) between intervention and control groups with 95% confidence interval (CI) were calculated using random-effects model. The Cochrane Collaboration's tool was used to assess the risk of bias. RESULTS: Thirteen randomized controlled trials met the inclusion criteria. Peer support resulted in a significant reduction in HbA1c (MD -0.57 [95% CI: -0.78 to -0.36]). Programs with moderate or high frequency of contact showed a significant reduction in HbA1c levels (MD -0.52 [95% CI: -0.60 to -0.44] and -0.75 [95% CI: -1.21 to -0.29], respectively), whereas programs with low frequency of contact showed no significant reduction (MD -0.32 [95% CI: -0.74 to 0.09]). The reduction in HbA1c were greater among patients with a baseline HbA1c ≥ 8.5% (MD -0.78 [95% CI: -1.06 to -0.51]) and between 7.5 ~ 8.5% (MD -0.76 [95% CI: -1.05 to -0.47]), than patients with HbA1c < 7.5% (MD -0.08 [95% CI: -0.32 to 0.16]). CONCLUSIONS: Peer support had a significant impact on HbA1c levels among patients with type 2 diabetes. Priority should be given to programs with moderate or high frequency of contact for target patients with poor glycemic control rather than programs with low frequency of contact that target the overall population of patients.

[Identification of nuclear localization signals of pseudorabies virus gene UL49].

Tegument protein VP22 is encoded by Pseudorabies Virus (PRV) UL49. To identify the nuclear localization signals of UL49, it is necessary to determine the transport mechanism and biological functions of the VP22 protein. In this study, we identified two nuclear localization signals from UL49, NLS1 (5RKTRVA ADETASGARRR21) and NLS2 (241PGRKGKV247). The functional nuclear localization signal (NLS) of UL49 was identified by constructing truncated or site-specific UL49 mutants. The deletion of both NLS1 and NLS2 abrogated UL49 nuclear accumulation, whereas the deletion of NLS1 or NLS2 did not. Therefore, both NLS1 and NLS2 are critical for the nuclear localization of UL49. And our resuts showed that NLS2 is more important in this regard.

Type 2 diabetes mellitus and risk of malignant melanoma: a systematic review and meta-analysis of cohort studies.

BACKGROUND: Epidemiology studies have demonstrated inconsistent associations between type 2 diabetes mellitus and the risk of malignant melanoma. To this end, the aim was to perform a meta-analysis of cohort studies. METHOD: Medline, PubMed, Embase and the Cochrane Library were searched up to February 2014. Cohort studies addressing the relative risk of type 2 diabetes mellitus on malignant melanoma were included in this meta-analysis. The Newcastle-Ottawa Scale was applied for quality evaluation. The pooled relative risks with the corresponding 95% confidence intervals (95% CIs) were calculated by using random-effects or random-effects model. Heterogeneity and publication bias were evaluated by I (2) and funnel plot analysis, respectively. Data was analyzed using STATA 11.0. RESULTS: A total of 9 independent cohorts from 8 manuscripts were entered this meta-analysis. Type 2 diabetes mellitus was slightly associated with an increased risk of malignant melanoma, and the pooled relative risk was 1.15 (95% CI, 1.00-1.32) in diabetes compared with non-diabetes with significant evidence of heterogeneity among these studies (P=0.016, I (2) =57.6%). For the studies adjusted for age, gender and obesity, the relative risks were 1.21 (95% CI, 1.03-1.42), 1.17 (95% CI, 1.01-1.35) and 1.11 (95% CI, 1.00-1.24), respectively. For the population-based studies in which case cohort established, the relative risk was 1.85 (95% CI, 1.31-2.62). CONCLUSION: Type 2 diabetes might be an independent risk factor for malignant melanoma. Further studies are needed to specifically test the effect, and fully elucidate the underlying pathophysiologic mechanisms.

Development of a group selective molecularly imprinted polymers based solid phase extraction of malachite green from fish water and fish feed samples.

A group selective molecularly imprinted solid phase extraction (MISPE) for malachite green (MG) from fish water and fish feed samples was developed. Using MG as template molecule, methacrylic acid as functional monomer, ethylene glycoldimethacrylate as linking agent and bulk polymerization as synthetic method, the molecularly imprinted polymers (MIPs) were synthesized and characterized with rebinding experiment. The Scatchard polt's analysis revealed that the template-polymer system showed the two-site binding behavior with dissociation constants of 0.3194 micromol L(-1) and 15.70 micromol L(-1), respectively. MG and two structurally related compounds, leucomalachite green (LMG) and crystal violet (CV) were employed for selectivity test. The MIPs exhibited the highest selective rebinding to MG, but also displayed 83.0% and 87.5% of cross-reactivity with LMG and CV, demonstrating that MIPs could be used as group recognition sorbents in solid phase extraction. The extraction conditions of MISPE column for MG were optimized. Tap water samples spiked with MG at concentration of 0.5-10 ng mL(-1) were extracted by MISPE column and analyzed by high performance liquid chromatography. The recoveries of MISPE column for MG extraction were found to be 76.8-93.7% with the relative standard deviations of 2.12-10.09%, indicating the feasibility of the prepared MIPs for MG extraction. No detectable MG was observed in one fish farming water sample and two fish feed samples; while the MG concentrations in two pet fishpond water samples were found at 1.50 ng mL(-1) and 0.67 ng mL(-1), respectively.