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Purpose: To explore mild cognitive dysfunction and/or spatial working memory impairment in patients with primary onset middle-age type 2 diabetes mellitus (T2DM] using ethology (behavior tests) and blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI)., Materials and Methods: Eighteen primary onset T2DM patients and 18 matched subjects with normal blood glucose levels were all tested using the Montreal cognitive assessment scale test, the Wechsler Memory Scale Chinese-revised test, and scanned using BOLD-fMRI (1.5T, EPI sequence) while performing the n-back task to find the activation intensity of some cognition-related areas., Results: The ethology results showed that T2DM patients had a mild cognitive impairment and memory dysfunction (P < 0.05). The fMRI scan identified a neural network consisting of bilateral dorsolateral prefrontal cortex (DLPFC), bilateral premotor area (PreMA), bilateral parietal lobe (PA), and anterior cingulate cortex (ACC) / supplementary motor area (SMA) that was activated during the n-back task, with right hemisphere dominance. However, only the right PA and ACC/SMA showed a load effect via quantitative analysis in the T2DM group; the activation intensity of most working memory-related brain areas for the T2DM group were lower than for the control group under three memory loads. Furthermore, we found that the activation intensity of some cognition-related areas, including the right insular lobe, left caudate nucleus, and bilateral hippocampus/parahippocampal gyrus were lower than the control group under the memory loads., Conclusion: Diabetes-related brain damage of primary onset middle-age T2DM patients with right DLPFC-posterior parietal lobe and parahippocampal gyrus default network causes impairment of spatial working memory and mild cognitive dysfunction., (© 2015 Wiley Periodicals, Inc.)

It is well established that developmental exposure of sevoflurane (an inhalational anesthetic) is capable of inducing neuronal apoptosis and subsequent learning and memory disorders. Synaptic NMDA receptors activity plays an essential role in cell survival, while the extra-synaptic NMDA receptors activation is usually associated with cell death. However, whether synaptic or extra-synaptic NMDA receptors mediate developmental sevoflurane neurotoxicity is largely unknown. Here, we show that developmental sevoflurane treatment decreased NR2A, but increased NR2B subunit expression both in vitro and in vivo. Sevoflurane-induced neuronal apoptosis was attenuated by synaptic NMDA receptors activation or low dose of exogenous NMDA in vitro. Interestingly, these effects could be abolished by NR2A inhibitor PEAQX, but not NR2B inhibitor Ifenprodil in vitro. In contrast, activation of extra-synaptic NMDA receptors alone had no effects on sevoflurane neurotoxicity. In the scenario of extra-synaptic NMDA receptors stimulation, however, sevoflurane-induced neuronal apoptosis could be prevented by addition of Ifenprodil, but not by PEAQX in vitro. In addition, sevoflurane neurotoxicity could also be rescued by memantine, an uncompetitive antagonist for preferential blockade of extra-synaptic NMDA receptors both in vitro and in vivo. Furthermore, we found that developmental sevoflurane-induced phospho-ERK1/2 inhibition was restored by synaptic NMDA receptor activation (in vitro), low dose of NMDA (in vitro) or memantine (in vivo). And the neuroprotective role of synaptic NMDA activity was able to be reversed by MEK1/2 inhibitor U0126 in vitro. Finally, administration of memantine or NMDA significantly improved spatial learning and memory dysfunctions induced by developmental sevoflurane exposure without influence on locomotor activity. These results indicated that activation of synaptic NR2A-containing NMDA receptors, or inhibition of extra-synaptic NR2B-containing NMDA receptors contributed to the relief of sevoflurane neurotoxicity, and the ERK1/2 MAPK signaling may be involved in this process.

We propose a new solution to flexibly generate the coherent rectangular pulse from an ultrafast fiber laser based on the dispersive Fourier transformation (DFT) technique. The rectangular dissipative soliton (DS) spectra emitted from a net-normal dispersion mode-locked fiber laser is mapped into a time-domain coherent rectangular waveform through the DFT technique. The rectangular pulse can be broadened flexibly with the adjustments of the pump power. The coherence and shot-to-shot fluctuations of the achieved rectangular pulses are further verified by the Mach-Zehnder interference experiment and the recorded single-shot pulse train, respectively. The results demonstrate that the combination of DS mode-locked laser and DFT technique might be indeed an effective and flexible way to achieve highly coherent rectangular pulses.

We reported on the generation of dissipative rogue waves (DRWs) induced by long-range chaotic multi-pulse interactions in a fiber laser based on a topological insulator (TI)-deposited microfiber photonic device. By virtue of the simultaneous saturable absorption effect and high nonlinearity provided by the TI-deposited microfiber, a localized, chaotic multi-pulse wave packet with strong long-range nonlinear interactions could be obtained, which gives rise to the formation of DRWs. The results might enhance the understanding of DRWs in optical systems, and further demonstrated that the TI-deposited microfiber could be considered as an excellent photonic device with both saturable absorption and highly nonlinear effects for the application field of nonlinear optics.

Background: Thermotherapy has been known to be one of the most effective adjuvants to radiotherapy (RT) in cancer treatment, but it is not widely implemented clinically due to some limitations, such as, inadequate temperature concentrations to the tumor tissue, nonspecific and non-uniform distribution of heat. So we constructed arginine-glycine-aspartate peptides-conjugated gold nanorods (RGD-GNRs) that target the alpha(v) beta(3) Integrin (αvβ3) and investigate whether the photo-thermal effect of RGD-GNRs by near infrared radiation (NIR) could enhance the efficiency of RT in melanoma cancer cells., Results: RGD-GNRs could be seen both on the surface of the cell membranes and cytoplasm of A375 cells with high expression of αvβ3. After exposed to 808 nm NIR, RGD-GNRs with various concentrations could be rapidly heated up. Compared to other treatments, flow cytometric analysis indicated that RT + NIR + RGD-GNRs increased apoptosis (p < 0.001) and decreased the proportion of cells in the more radioresistant S phase (p = 0.014). Treated with NIR + RGD-GNRs, the radiosensitivity was also significantly enhanced (DMFSF2: 1.41)., Conclusion: Results of the current study showed the feasibility of using RGD-GNRs for synergetic RT with photo-thermal therapy. And it would greatly benefit the therapeutic effects of refractory or recurrent malignant cancers.

Ultrafast fiber lasers play a significant role in our society with many aspects ranging from fundamental physics to industrial purposes. Searching for high-performance saturable absorbers (SAs) is vital to the developments of ultrafast fiber lasers. Gold nanorods (GNRs) have been discovered to possess saturable absorption effect. However, a major obstacle to make the GNRs as high-performance and practical SA is the low optical damage threshold. To overcome this drawback, herein we proposed the nanocomposites with gold nanorods/silica core-shell structure (GNRs@SiO(2)) as a high-performance SA for ultrashort pulse generation in a fiber laser. The GNRs@SiO(2) SA presents a modulation depth of 4.2% and nonsaturable loss of 45.6%. With the proposed GNRs@SiO(2) SA, 379 fs pulse was directly obtained from the fiber laser. The achieved results demonstrated that the GNR@SiO(2) could be indeed a good candidate of high-performance SA towards practical applications in the field of ultrafast photonics.

Purpose: To prepare chitosan/β-glycerophosphate salt (CS/β-GP) thermosensitive hydrogel membranes loaded enamel matrix proteins and detect the guided bone regeneration properties., Methods: A newly membrane was synthesized using thermal phase inversion property of the CS/ββ-GP system. The membrane was synthesized and added with protein BSA. The concentration of protein was detected at different time points by enhanced protein assay kit, and the protein release curve was drawn. CS/β-GP membrane added EMPs (1.0 g) as group A, CS/β-GP (1.0 g) membrane as group B and nothing as blank control group (group C). They were co-cultured with ST2 cells. The mechanical properties of the membranes were tested in vitro, and the compatibility properties were detected by MTT method. The activity of ALP was assayed by PNPP method. The data was analyzed by SPSS 16.0 software package., Results: Membranes with different concentration of CS/β-GP could release protein slowly more than 12 days, and the total quantity of the released protein increased with the concentration of the β-GP. The changes of mechanical properties of the membranes were not significant (P>0.05). The OD value of group A, B and C had statistically significant difference in the MTT test. The values of group A and B were higher than that of group C, while the value of group A was higher than that of group B (P<0.05). The activities of ALP were different in the three groups. The activities of group A and B were higher than that of the blank control group (P<0.05).The difference in expression of ALP between group A and B was also statistically significant. The expression in group A was higher than that in group B (P<0.05)., Conclusions: The new type CS/β-GP membrane shows property of guided bone regeneration in vitro, which have the potentials for clinical use.

Few-layer black phosphorus (BP), as the most alluring graphene analogue owing to its similar structure as graphene and thickness dependent direct band-gap, has now triggered a new wave of research on two-dimensional (2D) materials based photonics and optoelectronics. However, a major obstacle of practical applications for few-layer BPs comes from their instabilities of laser-induced optical damage. Herein, we demonstrate that, few-layer BPs, which was fabricated through the liquid exfoliation approach, can be developed as a new and practical saturable absorber (SA) by depositing few-layer BPs with microfiber. The saturable absorption property of few-layer BPs had been verified through an open-aperture z-scan measurement at the telecommunication band. The microfiber-based BP device had been found to show a saturable average power of ~4.5 mW and a modulation depth of 10.9%, which is further confirmed through a balanced twin detection measurement. By integrating this optical SA device into an erbium-doped fiber laser, it was found that it can deliver the mode-locked pulse with duration down to 940 fs with central wavelength tunable from 1532 nm to 1570 nm. The prevention of BP from oxidation through the "lateral interaction scheme" owing to this microfiber-based few-layer BP SA device might partially mitigate the optical damage problem of BP. Our results not only demonstrate that black phosphorus might be another promising SA material for ultrafast photonics, but also provide a practical solution to solve the optical damage problem of black phosphorus by assembling with waveguide structures such as microfiber.

We report on the generation of a high-repetition-rate pulse in a fiber laser using a graphene-deposited microfiber photonic device (GMPD) and a Fabry-Perot filter. Taking advantage of the unique nonlinear optical properties of the GMPD, dissipative four-wave mixing effect (DFWM) could be induced at low pump power. Based on DFWM mode-locking mechanism, the fiber laser delivers a 100 GHz repetition rate pulse train. The results indicate that the small sized GMPD offers an alternative candidate of highly nonlinear optical component to achieve high-repetition rate pulses, and also opens up possibilities for the investigation of other abundant nonlinear effects or related fields of photonics.

Ectopically expressed Cre recombinase in extrapancreatic tissues in RIP-Cre mice has been well documented. The objective of this study was to find a simple solution that allows for improved beta-cell specific targeting. To this end, the RIP-Cre and reporter CMV-loxP-DsRed-loxP-EGFP expression cassettes were configurated into a one-plasmid and two-plasmid systems, which labeled approximately 80% insulin-positive INS-1 cells after 48 h transfection. However, off-target labeling was robustly found in more than 15% insulin-negative Ad293 cells. When an IRES element was inserted in front of Cre to reduce the translation efficiency, the ratio of recombination between INS-1 and Ad293 cells increased 3-4-fold. Further, a series of Cre mutants were generated by site-directed mutagenesis. When one of the mutants, Cre(H289P) in both configurations, was used in the experiment, the percentage of recombination dropped to background levels in a number of insulin-negative cell lines, but decreased only slightly in INS-1 cells. Consistently, DNA substrate digestion assay showed that the enzymatic activity of Cre(H289P) was reduced by 30-fold as compared to that of wild-type. In this study, we reported the generation of constructs containing RIP and Cre mutants, which enabled enhanced beta-cell specific labeling in vitro. These tools could be invaluable for beta-cell targeting and to the study of islet development.

We report on the trapping of noise-like pulse in a figure-eight fiber laser mode locked by nonlinear amplifier loop mirror (NALM). After achievement of noise-like vector pulse, it was found that the wavelength shift of the two resolved polarization components responsible for the pulse trapping was very sensitive to the cavity birefringence. By properly rotating the polarization controllers (PCs), the wavelength shift could be up to 4.8 nm, which is much larger than that of conventional soliton trapping. The observed results would shed some light on the fundamental physics of noise-like pulse as well as its vector features in fiber lasers.

Background: Because guanine-based herpes simplex virus thymidine kinase inhibitors are not orally available, we synthesized various 6-deoxy prodrugs of these compounds and evaluated them with regard to solubility in water, oral bioavailability, and efficacy to prevent herpes simplex virus-1 reactivation from latency in a mouse model., Methods: Organic synthesis was used to prepare compounds, High Performance Liquid Chromatography (HPLC) to analyze hydrolytic conversion, Mass Spectrometry (MS) to measure oral bioavailability, and mouse latent infection and induced reactivation to evaluate the efficacy of a specific prodrug., Results: Aqueous solubilities of prodrugs were improved, oxidation of prodrugs by animal cytosols occurred in vitro, and oral absorption of the optimal prodrug sacrovir™ (6-deoxy-mCF3PG) in the presence of the aqueous adjuvant Soluplus® and conversion to active compound N(2)-[3-(trifluoromethyl)pheny])guanine (mCF3PG) were accomplished in mice. Treatment of herpes simplex virus-1 latent mice with sacrovir™ in 1% Soluplus in drinking water significantly suppressed herpes simplex virus-1 reactivation and viral genomic replication., Conclusions: Ad libitum oral delivery of sacrovir™ was effective in suppressing herpes simplex virus-1 reactivation in ocularly infected latent mice as measured by the numbers of mice shedding infectious virus at the ocular surface, numbers of trigeminal ganglia positive for infectious virus, number of corneas that had detectable infectious virus, and herpes simplex virus-1 genome copy numbers in trigeminal ganglia following reactivation. These results demonstrate the statistically significant effect of the prodrug on suppressing herpes simplex virus-1 reactivation in vivo., (© The Author(s) 2015.)

Introduction: long non-coding RNAs (lncRNAs) are emerging as new regulators in the cancer paradigm, the involvement of lncRNAs in urothelial carcinoma of the bladder (UCB) is just beginning to be studied. In this study, we focused on lncRNA SPRY4-IT1 and investigated its expression pattern, clinical significance, and biological function in UCB., Methods: SPRY4-IT1 expression in UCB tissues was examined by quantitative Real-time PCR (qRT-PCR) and its correlation with clinicopathological features and patient prognosis was later analyzed. Moreover, in vitro assays were performed to explore its role in bladder cancer progression., Results: SPRY4-IT1 expression was elevated in UCB tissues, and SPRY4-IT1 levels were highly positively correlated with histological grade, tumor stage, and lymph node metastasis and reduced overall survival. A multivariate analysis showed that SPRY4-IT1 expression is an independent prognostic factor of overall survival in patients with UCB. Additionally, the results of in vitro assays showed that the suppression of SPRY4-IT1 expression in bladder cancer cells significantly inhibit cell proliferation, migration, and invasion., Conclusions: Our data suggested that lncRNA SPRY4-IT1 is a novel molecule involved in bladder cancer progression, which provide a potential prognostic biomarker and therapeutic target.

As a kind of environmental endocrine disruptors, bisphenol A received a wide attention around the world. The planar waveguide fluorescent biosensor can rapidly and sensitively detect traceable bisphenol A in water samples. Under the optimized test conditions, the typical calibration curve for BPA determination by the biosensor showed a detection limit of (0.04 +/- 0.007) microg x L(-1) The linear response ranged from 0.16 microg x L(-1) to 22.40 microg x L(-1). The 50% inhibition concentration (IC50) was (1.67 +/- 0.47) microg x L(-1). By means of adding 0.5% EDTA to sample solutions could weaken the interference of water hardness. Under the optimal conditions, the recovery ratios for four kinds of real water samples were in the range of 88% to 111%, with R.S.D. less than 15%. The results indicate that this method features the potential in the practical detections of bisphenol A in real water samples.

We reported on the generation of versatile soliton molecules in a fiber laser mode-locked by a microfiber-based graphene saturable absorber (GSA). By virtue of the highly nonlinear effect of the microfiber-based GSA, the soliton molecules could be easily observed. In addition to regular soliton molecules, it is found that the "soliton atoms" in molecules could exhibit different characteristics and show ultra-narrow pulse separations, which was termed as 'structural soliton molecule'. The pulse profiles of 'structural soliton molecules' were further reconstructed theoretically. The obtained results would give further insight towards understanding the dynamics of soliton molecules in fiber lasers.

We reported on the generation of high-order harmonic mode-locking in a fiber laser using a microfiber-based molybdenum disulfide (MoS(2)) saturable absorber (SA). Taking advantage of both the saturable absorption and large third-order nonlinear susceptibilities of the few-layer MoS(2), up to 2.5 GHz repetition rate HML pulse could be obtained at a pump power of 181 mW, corresponding to 369th harmonic of fundamental repetition frequency. The results provide the first demonstration of the simultaneous applications of both highly nonlinear and saturable absorption effects of the MoS(2), indicating that the microfiber-based MoS(2) photonic device could serve as high-performance SA and highly nonlinear optical component for application fields such as ultrafast nonlinear optics.

We report on the generation of a femtosecond pulse in a fiber ring laser by using a polyvinyl alcohol (PVA)-based molybdenum disulfide (MoS(2)) saturable absorber (SA). With a saturable optical intensity of 34  MW/cm(2) and a modulation depth of ∼4.3%, the PVA-based MoS(2) SA had been employed with an erbium-doped fiber ring laser as a mode locker. The mode-locking operation could be achieved at a low pump threshold of 22 mW. A ∼710  fs pulse centered at 1569.5 nm wavelength with a repetition rate of 12.09 MHz had been achieved with proper cavity dispersion. With the variation of net cavity dispersion, output pulses with durations from 0.71 to 1.46 ps were obtained. The achievement of a femtosecond pulse at 1.55 μm waveband demonstrates the broadband saturable absorption of MoS(2), and also indicates that the filmy PVA-based MoS(2) SA is indeed a good candidate for an ultrafast saturable absorption device.

The vector nature of multi-soliton dynamic patterns was investigated in a passively mode-locked figure-eight fiber laser based on the nonlinear amplifying loop mirror (NALM). By properly adjusting the cavity parameters such as the pump power level and intra-cavity polarization controllers (PCs), in addition to the fundamental vector soliton, various vector multi-soliton regimes were observed, such as the random static distribution of vector multiple solitons, vector soliton cluster, vector soliton flow, and the state of vector multiple solitons occupying the whole cavity. Both the polarization-locked vector solitons (PLVSs) and the polarization-rotating vector solitons (PRVSs) were observed for fundamental soliton and each type of multi-soliton patterns. The obtained results further reveal the fundamental physics of multi-soliton patterns and demonstrate that the figure-eight fiber lasers are indeed a good platform for investigating the vector nature of different soliton types.

We reported on the generation of dual-wavelength rectangular pulses in a Yb-doped fiber laser (YDFL) by using a microfiber-based graphene saturable absorber (GSA). The duration of dual-wavelength rectangular pulse could be varied from 1.41 ns to 4.23 ns with the increasing pump power. With a tunable bandpass filter, it was found that the characteristics of the rectangular pulses centered at 1061.8 nm and 1068.8 nm are similar to each other. Moreover, the dual-wavelength switchable operation was also realized by properly rotating the polarization controllers (PCs). The demonstration of the dual-wavelength rectangular pulses from a YDFL would open some applications for fields such as spectroscopy, biomedicine and sensing research.

Objective: It is known that noxious stimuli from inflamed tissue may increase the excitability of spinal dorsal horn neurons (a process known as central sensitization), which can signal back and contribute to peripheral inflammation. However, the underlying mechanisms have yet to be fully defined. A number of recent studies have indicated that spinal NF-κB/p65 is involved in central sensitization, as well as pain-related behavior. Thus, the aim of this study was to determine whether NF-κB/p65 can facilitate a peripheral inflammatory response in rat adjuvant-induced arthritis (AIA)., Methods: Lentiviral vectors encoding short hairpin RNAs that target NF-κB/p65 (LV-shNF-κB/p65) were constructed for gene silencing. The spines of rats with AIA were injected with LV-shNF-κB/p65 on day 3 or day 10 after treatment with Freund's complete adjuvant (CFA). During an observation period of 20 days, pain-related behavior, paw swelling, and joint histopathologic changes were evaluated. Moreover, the expression levels of spinal tumor necrosis factor α (TNFα), interleukin-1β (IL-1β), and cyclooxygenase 2 (COX-2) were assessed on day 14 after CFA treatment., Results: The presence of peripheral inflammation in rats with AIA induced an increase in NF-κB/p65 expression in the spinal cord, mainly in the dorsal horn neurons and astrocytes. Delivery of LV-shNF-κB/p65 to the spinal cord knocked down the expression of NF-κB/p65 and significantly attenuated hyperalgesia, paw edema, and joint destruction. In addition, spinal delivery of LV-shNF-κB/p65 reduced the overexpression of spinal TNFα, IL-1β, and COX-2., Conclusion: These findings indicate that spinal NF-κB/p65 plays an important role in the initiation and development of both peripheral inflammation and hyperalgesia. Thus, inhibition of spinal NF-κB/p65 expression may provide a potential treatment to manage painful inflammatory disorders., (Copyright © 2014 by the American College of Rheumatology.)

We reported on the generation of femtosecond pulse in a fiber ring laser by using a polyvinyl alcohol (PVA)-based topological insulator (TI), Bi2Se3 saturable absorber (SA). The PVA-TI composite has a low saturable optical intensity of 12 MW/cm2 and a modulation depth of ~3.9%. By incorporating the fabricated PVA-TISA into a fiber laser, mode-locking operation could be achieved at a low pump threshold of 25 mW. After an optimization of the cavity parameters, optical pulse with ~660 fs centered at 1557.5 nm wavelength had been generated. The experimental results demonstrate that the PVA could be an excellent host material for fabricating high-performance TISA, and also indicate that the filmy PVA-TISA is indeed a good candidate for ultrafast saturable absorption device.

Edema, as one of common clinical diseases, could be treated by taking medicines and adopting external therapies with traditional Chinese medicines (TCM). In recent years, there have been many clinical and basic studies concerning external therapies with TCM on edema Data showed that the external therapies are mostly composed of such purgating drugs as Rhei Radix et Rhizoma, Natrii Sulfas and Pharbitidis Semen, heat-clearing drug such as Phellodendri Chinensis Cortex and resuscitation-inducing drug such as Borneolum Syntheticum. The study showed that ingredients of external therapies did not pass through hilum and hepatic system, and thus avoided the first pass effect of livers. They enabled effective components of drugs to be rapidly absorbed through pores and skins, strengthened the effect against edema, shortened the treatment course, decreased side effects, and were convenient and inexpensive. External therapies with TCM could play unique advantages in inhibiting edema in the future clinical studies.

We report on the generation of passive harmonic mode locking of a fiber laser using a microfiber-based topological insulator (TI) Bi(2)Te(3) saturable absorber (SA). The optical deposition method was employed to fabricate the microfiber-based TISA. By virtue of the excellent nonlinear optical property of the proposed TISA, the fiber laser could operate at the pulse repetition rate of 2.04 GHz under a pump power of 126 mW, corresponding to the 418th harmonic of fundamental repetition frequency. The results demonstrate that the microfiber-based TI photonic device can operate as both the high nonlinear optical component and the SA in fiber lasers, and could also find other applications in the related fields of photonics.

We reported on the dissipative soliton resonance (DSR) phenomenon in a mode-locked Yb-doped fiber laser by using the nonlinear polarization rotation technique. It was found that the multi-pulse oscillation under high pump power could be circumvented by properly adjusting the polarization controllers, namely, the wave-breaking-free rectangular pulse in DSR region was achieved. As the DSR signature, the pulse duration varied from 8.8 ps to 22.92 ns with the increasing pump power. Correspondingly, the maximum pulse energy was 3.24 nJ. The results demonstrated that the DSR phenomenon could exist in Yb-doped fiber lasers, which could be used to achieve wave-breaking-free, ultrahigh-energy pulse.

Background Aims: Research results have shown that bone mesenchymal stromal cells (BMSC) can different into neural cells. Electromagnetic fields (EMF) play a role in regulating cell proliferation and differentiation, but the mechanisms behind this are unknown. In the present study, we explored the efficacy of EMF on the induction of rat BMSC differentiation into neurons in vitro., Methods: First, rat BMSC were induced in a nerve cell culture environment and divided into three groups: an EMF induction treatment group (frequency of 50 Hz, magnetic induction of 5 mT, 60 min per day for 12 days), an induction-only group and a control group. Second, we observed cell phenotypes in a confocal microscope, tested gene expression through the use of reverse transcriptase-polymerase chain reaction, and detected postsynaptic currents by means of a cell patch-clamp. We analyzed the cell cycles and the portion of cells expressing neural cell markers with the use of flow cytometry., Results: The results indicated that EMF can facilitate BMSC differentiation into neural cells, which expressed neuronal-specific markers and genes; they formed synaptic junctions and pulsed excitatory postsynaptic currents. At the same time, the G0-G1 phase ratio recorded by means of flow cytometry gradually decreased under the EMF treatment, whereas there was an increase of S-phase ratio, and the portion of cells expressing neuronal-specific markers increased., Conclusions: Given that a noninvasive treatment of 50-Hz EMF could significantly facilitate BMSC to differentiate into functional neurons, EMF appears to be a promising clinical option for stem cell transplantation therapies to combat central nervous system diseases., (Copyright © 2013 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Background: To evaluate the role of γ-H2AX in peripheral blood lymphocytes (PBLs) as a predictive biomarker of the severity of oral mucositis (OM) in head and neck cancer (HNC) patients with receiving radiotherapy., Methods: In vitro assays for evaluating DNA damage and repair kinetics were performed on blood samples withdrawn from 25 HNC patients undergoing radiotherapy or chemoradiotherapy before radiotherapy. As for the in vivo study, blood samples were also withdrawn before radiotherapy, and 1 hour after radiotherapy on the fourth and last days. Flow cytometry was used to assess the expression of γ-H2AX in PBLs. OM was assessed using the World Health Organization (WHO) scores twice a week and correlated with the expression of γ-H2AX., Results: The in vitro assay results showed that patients with severe OM had higher γ-H2AX-specific relative fluorescence at various irradiation doses in the damage kinetics assay, with significantly higher γ-H2AX expression at 8 Gy (p = 0.039), and also at 24 hours after irradiation at a dose of 2 Gy in the repair kinetics assay, compared to the patients with mild OM (p = 0.008). The optimal cutoff value for relative fluorescence of γ-H2AX was 0.960, 24 hours post-irradiation. However, there were no significant differences in γ-H2AX expression at different times between the two groups, as assessed with the in vivo assay., Conclusions: These results suggest that the damage and repair kinetics of γ-H2AX from PBLs in the in vitro study may have predictive value for identifying the grades of OM among HNC patients prior to radiotherapy.

Background: Over-expression of epidermal growth factor receptor (EGFR) or insulin-like growth factor-1 receptor (IGF-1R) have been shown to closely correlate with radioresistance of breast cancer cells. This study aimed to investigate the impact of co-inhibition of EGFR and IGF-1R on the radiosensitivity of two breast cancer cells with different profiles of EGFR and IGF-1R expression., Methods: The MCF-7 (EGFR +/-, IGF-1R +++) and MDA-MB-468 (EGFR +++, IGF-1R +++) breast cancer cell lines were used. Radiosensitizing effects were determined by colony formation assay. Apoptosis and cell cycle distribution were measured by flow cytometry. Phospho-Akt and phospho-Erk1/2 were quantified by western blot. In vivo studies were conducted using MDA-MB-468 cells xenografted in nu/nu mice., Results: In MDA-MB-468 cells, the inhibition of IGF-1R upregulated the p-EGFR expression. Either EGFR (AG1478) or IGF-1R inhibitor (AG1024) radiosensitized MDA-MB-468 cells. In MCF-7 cells, radiosensitivity was enhanced by AG1024, but not by AG1478. Synergistical radiosensitizing effect was observed by co-inhibition of EGFR and IGF-1R only in MDA-MB-468 cells with a DMF10% of 1.90. The co-inhibition plus irradiation significantly induced more apoptosis and arrested the cells at G0/G1 phase in MDA-MB-468 cells. Only co-inhibition of EGFR and IGF-1R synergistically diminished the expression of p-Akt and p-Erk1/2 in MDA-MB-468 cells. In vivo studies further verified the radiosensitizing effects by co-inhibition of both pathways in a MDA-MB-468 xenograft model., Conclusion: Our data suggested that co-inhibition of EGFR and IGF-1R synergistically radiosensitized breast cancer cells with both EGFR and IGF-1R high expression. The approach may have an important therapeutic implication in the treatment of breast cancer patients with high expression of EGFR and IGF-1R.

Background: Toll-like receptors (TLRs) play a pivotal role in the defense against invading pathogens by detecting pathogen-associated molecular patterns (PAMPs). TLR4 recognizes lipopolysaccharides (LPS) in the cell walls of Gram-negative bacteria, resulting in the induction and secretion of proinflammatory cytokines such as TNF-α and IL-6. The WW domain containing E3 ubiquitin protein ligase 1 (WWP1) regulates a variety of cellular biological processes. Here, we investigated whether WWP1 acts as an E3 ubiquitin ligase in TLR-mediated inflammation., Methodology/results: Knocking down WWP1 enhanced the TNF-α and IL-6 production induced by LPS, and over-expression of WWP1 inhibited the TNF-α and IL-6 production induced by LPS, but not by TNF-α. WWP1 also inhibited the IκB-α, NF-κB, and MAPK activation stimulated by LPS. Additionally, WWP1 could degrade TRAF6, but not IRAK1, in the proteasome pathway, and knocking down WWP1 reduced the LPS-induced K48-linked, but not K63-linked, polyubiquitination of endogenous TRAF6., Conclusions/significance: We identified WWP1 as an important negative regulator of TLR4-mediated TNF-α and IL-6 production. We also showed that WWP1 functions as an E3 ligase when cells are stimulated with LPS by binding to TRAF6 and promoting K48-linked polyubiquitination. This results in the proteasomal degradation of TRAF6.

Background: Amyotrophic lateral sclerosis (ALS), partly caused by the mutations and aggregation of human copper, zinc superoxide dismutase (SOD1), is a fatal degenerative disease of motor neurons. Because SOD1 is a major copper-binding protein present at relatively high concentration in motor neurons and copper can be a harmful pro-oxidant, we want to know whether aberrant copper biochemistry could underlie ALS pathogenesis. In this study, we have investigated and compared the effects of cupric ions on the aggregation of ALS-associated SOD1 mutant A4V and oxidized wild-type SOD1., Methodology/principal Findings: As revealed by 90° light scattering, dynamic light scattering, SDS-PAGE, and atomic force microscopy, free cupric ions in solution not only induce the oxidation of either apo A4V or Zn2-A4V and trigger the oligomerization and aggregation of oxidized A4V under copper-mediated oxidative conditions, but also trigger the aggregation of non-oxidized form of such a pathogenic mutant. As evidenced by mass spectrometry and SDS-PAGE, Cys-111 is a primary target for oxidative modification of pathological human SOD1 mutant A4V by either excess Cu(2+) or hydrogen peroxide. The results from isothermal titration calorimetry show that A4V possesses two sets of independent binding sites for Cu(2+): a moderate-affinity site (10(6) M(-1)) and a high-affinity site (10(8) M(-1)). Furthermore, Cu(2+) binds to wild-type SOD1 oxidized by hydrogen peroxide in a way similar to A4V, triggering the aggregation of such an oxidized form., Conclusions/significance: We demonstrate that excess cupric ions induce the oxidation and trigger the aggregation of A4V SOD1, and suggest that Cu(2+) plays a key role in the mechanism of aggregation of both A4V and oxidized wild-type SOD1. A plausible model for how pathological SOD1 mutants aggregate in ALS-affected motor neurons with the disruption of copper homeostasis has been provided.

Prion diseases and prion-like protein misfolding diseases involve the accumulation of abnormally aggregated forms of the normal host proteins, such as prion protein and Tau protein. These proteins are special because of their self-duplicating and transmissible characteristics. Such abnormally aggregated proteins mainly formed in neurons, cause the neurons dysfunction, and finally lead to invariably fatal neurodegenerative diseases. Prion diseases appear not only in animals, such as bovine spongiform encephalopathy in cattle and scrapie in sheep, but also in humans, such as Creutzfeldt-Jacob disease, and even the same prion or prion-like proteins can have many different phenotypes. A lot of biological evidence has suggested that the molecular basis for different strains of prions could be hidden in protein conformations, and the misfolded proteins with conformations different from the normal proteins have been proved to be the main cause for protein aggregation. Crowded physiological environments can be imitated in vitro to study how the misfolding of these proteins leads to the diseases in vivo. In this review, we provide an overview of the existing structural information for prion and prion-like proteins, and discuss the post-translational modifications of prion proteins and the difference between prion and other infectious pathogens. We also discuss what makes a misfolded protein become an infectious agent, and show some examples of prion-like protein aggregation, such as Tau protein aggregation and superoxide dismutase 1 aggregation, as well as some cases of prion-like protein aggregation in crowded physiological environments.

We report on the vector nature of rectangular pulse operating in dissipative soliton resonance (DSR) region in a passively mode-locked fiber laser. Apart from the typical signatures of DSR, the rectangular pulse trapping of two polarization components centered at different wavelengths was observed and they propagated as a group-velocity locked vector soliton. Moreover, the polarization resolved soliton spectra show different spectral distributions. The observed results will enhance the understanding of fundamental physics of DSR phenomenon.

Sirtuin 1 (SIRT1) is one member of the silent information regulator 2 (Sir2)-like family of proteins involved in glucose homeostasis in mammals. It has been reported that SIRT1 modulates endocrine signaling of glucose and fat homeostasis by regulating transcription factors such as forkhead transcription factor 3a (FOXO3a), glucose transporter 4 (GLUT4), peroxisome proliferator-activated receptor gamma (PPARγ) and PPARγ coactivator (PGC-1α). However, it is still not clear how SIRT1 is involved in the development of insulin resistance. To determine the location and expression of SIRT1 and its target proteins in rats and analyze the interactions and functions of these proteins in insulin resistance. Forty-eight male Sprague-Dawley rats were randomly divided into four regimen groups: normal control (NC), calorie restriction (CR), high-fat (HFa), and high-fructose (HFr). Animals were fed for 12 weeks and blood samples collected from tail veins at weeks 2, 4, 6, 8 and 12 after fasting for 16 h. Baseline metabolic parameters such as fasting blood sugar, insulin, cholesterol and triglycerides were analyzed. A glucose tolerance test was carried out at the end of the study. Visceral fat, consisting of epididymis and perirenal fat, was isolated and weighed. The pancreas from each animal was also immediately removed. Immunohistochemical staining was performed to detect the locations of SIRT1, FOXO3a, GLUT4, PPARγ and PGC-1α in the β-cell of the rat pancreas. Expression in the pancreas was analyzed by western blotting. Blood biochemical analysis indicated that the HFa and HFr groups were insulin-resistant. Immunohistochemical staining showed that GLUT4 was a nuclear protein. SIRT1, FOXO3a, PPARγ and PGC-1α were present in both the nucleus and the cytoplasm of β-cells of pancreatic islets. The expression of SIRT1, GLUT4 and PGC-1α increased significantly in response to CR, but decreased in the HFr and HFa groups. FOXO3a was similar in the CR and the NC groups, whereas it declined in the HFa and HFr groups. PPARγ was elevated in the HFa group, but dropped in the CR and HFr groups. These data suggest that SIRT1 and its regulators are involved in the development of insulin resistance.

The generation of mode-locked rectangular pulses operating in dissipative soliton resonance (DSR) region is demonstrated in an erbium-doped figure-eight fiber laser with net anomalous dispersion. The duration of the wave-breaking-free rectangular pulse broadens with the increase of pump power. At a maximum pump power of 341 mW, the pulse energy can be up to 3.25 nJ with a repetition rate of 3.54 MHz. Particularly, the spectrum of rectangular pulse operating in DSR exhibits conventional soliton sidebands. The observed results show that the formation of pulse operating in DSR region is independent of mode-locking techniques, which may be helpful for further understanding the DSR phenomenon.

Aberrant activation and dysfunction of the EGFR/PI3K/Akt signaling pathways are commonly reported in breast cancer. Constitutive activation of the PI3K/Akt pathway by the lack of PTEN regulation is associated with resistance to novel targeted therapies including EGFR inhibitors. We aimed to study whether Ly294002, an inhibitor of PI3K, could enhance the cytotoxicity of AG1478, an inhibitor of EGFR, on breast cancer cells. We tested these agents in the MDA-MB-468 and MCF-7 breast cancer cell lines with different EGFR and PTEN profiles (MDA-MB-468: high expression of EGFR and PTEN mutation; MCF-7: low expression of EGFR and PTEN wild type). Simultaneous inhibition of EGFR and PI3K in MDA-MB-468 cells with combined Ly294002 and AG1478 treatment had a greater anti-proliferative effect and increased mitotic death than either treatment alone. In addition, more apoptosis and increased induction of cell arrest at G0/G1 phase were observed in MDA-MB-468 cells with the combined treatment. Phosphor-EGFR and its downstream signal transducer, phosphor-Akt, were fully attenuated only by simultaneous treatment with Ly294002 and AG1478. These data suggest that the inhibition of PI3K could enhance the cytotoxicity of EGFR inhibitors on breast cancer cells and tumors which overexpress EGFR and demonstrate mutated PTEN. This dual inhibition treatment protocol may have important therapeutic implication in the treatment of a subset of breast cancer patients with high expression of EGFR and deficient function of PTEN.

The pulse dynamics operating in dissipative soliton resonance (DSR) region is experimentally investigated in a fiber ring laser. With the increase of pump power, the pulse profile transit from sech-like to rectangular shape was observed. The generated pulse in DSR region exhibits the conventional soliton spectrum with sideband generation. The duration-tuning range of the rectangular pulse is up to the cavity roundtrip time. Particularly, during the process of pulse duration broadening it was found that the rectangular pulse would trap a weak pulse generated from cw background. The obtained results may be useful for better understanding the DSR phenomenon.

Purpose: This study is to investigate the effects of electromagnetic fields (EMF) on proliferation of epidermal stem cells (ESC), which could present a viable clinical option for skin tissue engineering., Materials and Methods: The ESC obtained from human foreskin were grafted into type-I three-dimensional collagen sponge scaffolds, and then were exposed with EMF (frequency 50 Hz, intensity 5 mT) for 14 d (30 min per d). Meanwhile, the control group was set under the same conditions without EMF. The effects of EMF on growth and proliferation of ESC were analyzed with staining of hematoxylin and eosin (H&E) and 4',6-diamidino-2-phenylindole (DAPI) under microscope or scanning electron microscope. The data of DAPI staining for 2 d, 7 d, 10 d and 14 d were collected respectively to investigate the cells proliferation., Results: ESC cultured in collagen sponge scaffolds could be steady grown and EMF could promote ESC proliferation compared with control (P < 0.05)., Conclusions: EMF could significantly promote proliferation of ESC, which leads to a promising clinical option for skin tissue engineering.

Purpose: Mutations in the epidermal growth factor receptor (EGFR)/phosphoinositide 3-kinase (PI3K)/Akt signaling transduction pathway are common in cancer. This pathway is imperative to the radiosensitivity of cancer cells. We aimed to investigate the radiosensitizing effects of the simultaneous inhibition of EGFR and PI3K in breast cancer cells., Methods and Materials: MCF-7 cell lines with low expression of EGFR and wild-type PTEN and MDA-MB-468 cell lines with high expression of EGFR and mutant PTEN were used. The radiosensitizing effects by the inhibition of EGFR with AG1478 and/or PI3K with Ly294002 were determined by colony formation assay, Western blot was used to investigate the effects on downstream signaling. Flow cytometry was used for apoptosis and cell cycle analysis. Mice-bearing xenografts of MDA-MB-468 breast cancer cells were also used to observe the radiosensitizing effect., Results: Simultaneous inhibition of EGFR and PI3K greatly enhanced radiosensitizing effect in MDA-MB-468 in terms of apoptosis and mitotic death, either inhibition of EGFR or PI3K alone could enhance radiosensitivity with a dose-modifying factor (DMF(SF2)) of 1.311 and 1.437, radiosensitizing effect was further enhanced by simultaneous inhibition of EGFR and PI3K with a DMF(SF2) at 2.698. DNA flow cytometric analysis indicated that dual inhibition combined with irradiation significantly induced G0/G1 phase arrest in MDA-MB-468 cells. The expression of phosphor-Akt and phosphor-Erk1/2 (induced by irradiation and PI3K inhibitor) were fully attenuated by simultaneous treatment with both inhibitors in combination with irradiation. In addition, dual inhibition combined with irradiation induced dramatic tumor growth delay in MDA-MB-468 xenografts., Conclusions: Our study indicated that simultaneous inhibition of EGFR and PI3K could further sensitize the cancer cells to irradiation compared to the single inhibitor with irradiation in vitro and in vivo. The approach may have important therapeutic implication in the treatment of a subset of breast cancer patients with high expression of EGFR and deficient function of PTEN., (Copyright © 2012 Elsevier Inc. All rights reserved.)

N(2)-(3,4-Dichlorobenzyl)-7-(2-[1-morpholinyl]ethyl)guanine (MorE-DCBG, 362E) is a synthetic purine that selectively inhibits the replication-specific DNA polymerase of Clostridium difficile. MorE-DCBG and its analogs strongly inhibited the growth of a wide variety of C. difficile strains. When administered orally in a hamster model of C. difficile-specific colitis, 362E was as effective as oral vancomycin, the current agent of choice for treating severe forms of the human disease.

Based on the finding that aerobic Gram-positive antibacterials that inhibit DNA polymerase IIIC (pol IIIC) were potent inhibitors of the growth of anaerobic Clostridium difficile (CD) strains, we chose to clone and express the gene for pol IIIC from this organism. The properties of the recombinant enzyme are similar to those of related pol IIICs from Gram-positive aerobes, e.g. B. subtilis. Inhibitors of the CD enzyme also inhibited B. subtilis pol IIIC, and were competitive with respect to the cognate substrate 2'-deoxyguanosine 5'-triphosphate (dGTP). Significantly, several of these inhibitors of the CD pol IIIC had potent activity against the growth of CD clinical isolates in culture.

Objective: To investigate the influence of surface modification of titanium on OPG/RANKL mRNA expression in human osteoblast-like cells., Methods: MG-63 osteoblast-like cells were seeded on the titanium plates with surface polishing and with surface modification by sandblasting plus acid-base treatment, with the cells on glass slides as the control. On days 2, 4, 6, and 8 following cell seeding, the cells were harvested for examination of OPG/RANKL mRNA expression using RT-PCR and real-time PCR., Results: The expression of OPG/RANKL mRNA was sensitive to the surface microphotography. Compared with the other groups, the cells on the titanium plates with sandblasting plus acid-base treatment, which resulted in a porous micro-structure and high roughness, showed significantly up-regulated expression of OPG mRNA. OPG mRNA expression also showed a time-dependent up-regulation, and was the highest on day 8. The expression of the RANKL mRNA in cells on both of the titanium plates was higher than that in the control cells. The peak level of RANKL mRNA expression occurred on day 6 followed by a gradual decrease., Conclusion: A rough and porous surface of the culture plates and prolonged culture time can synergistically up-regulate the ratio of OPG/RANKL mRNA.

Several 2-anilino- and 2-benzylamino-3-deaza-6-oxopurines [3-deazaguanines] and selected 8-methyl and 8-aza analogs have been synthesized. 7-Substituted N(2)-(3-ethyl-4-methylphenyl)-3-deazaguanines were potent and selective inhibitors of Gram+ bacterial DNA polymerase (pol) IIIC, and 7-substituted N(2)-(3,4-dichlorobenzyl)-3-deazaguanines were potent inhibitors of both pol IIIC and pol IIIE from Gram+ bacteria, but weakly inhibited pol IIIE from Gram- bacteria. Potent enzyme inhibitors in both classes inhibited the growth of Gram+ bacteria (MICs 2.5-10μg/ml), and were inactive against the Gram- organism Escherichia coli. Several derivatives had moderate protective activity in Staphylococcus aureus-infected mice., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

We propose and demonstrate a highly flexible fiber laser capable of generating stable multiwavelength picosecond and single wavelength femtosecond pulses by using a semiconductor saturable absorber mirror and a contrast ratio tunable comb filter. In the multiwavelength lasing regime, up to 11-wavelength stable mode-locked pulses in 3 dB bandwidth with a channel spacing of 0.8 nm were obtained. While in the single wavelength with broadband spectrum lasing regime, the fiber laser emitted 576 fs soliton pulse. Through changing the contrast ratio of the comb filter, the conversion between the multiwavelength picosecond and single wavelength femtosecond pulsed operations could be efficiently achieved.

A higher expression of S-100 in tissue of thyroid papillary carcinoma (TPC) vs. thyroid follicular adenoma (TFA) (p < .001) was observed as well as a higher expression of CD83 in the peri-cancerous tissues vs. TFA (p < .001), oppositely, CD83 was negative in the cancerous net. TPC showed greater decreases in levels of CD80 and CD86 than did the TFA. These findings suggest that impaired immune function, absence of CD83-positive mature and activated dendritic cells in cancer nodules may have a role in the pathogenesis of TPC. The low expression of CD80 and CD86 in TPC may help them evade the immune system.

The aim was to investigate the prevalence of Herpes simplex virus (HSV)-2 infection among pregnant women in southern China and analyze the relationship between the HSV-2 infection and pregnancy outcome. We examined 1740 sera collected from pregnant women aged 21-39 years, using enzyme-linked immunosorbent assay for the detection of specific antibodies against HSV-2. The overall prevalence of HSV-2 infection was 23.56% (95% confidence interval [CI]=21.53-26.00). The prevalence of HSV-2 infection in the women with abnormal pregnancy was 35.93% (95% CI=26.23-42.44) (83/231), which was much higher than that in women who had been pregnant before but without abnormal pregnancy and that in the primipara group. (P<0.05). The presence of HSV-2 antibodies was also associated with status of education. The prevalence of HSV-2 infection in the 26-30-year age group (27.49%) (95% CI=24.53-30.33) was the highest among all age groups. The prevalence of HSV-2 infection in pregnant women in southern China is quite high. Women with asymptomatic or subclinical genital infection should be identified by examining the HSV-2 antibody, which would be helpful to reduce the abnormal pregnancy outcome., (© 2010 Japanese Dermatological Association.)

In this paper, we investigate the critical conditions of control light for a silicon-based photonic crystal bistable switching. By establishing a time-dependent evolution equation, the critical pump power and pump time of the control light are derived, respectively. It is found that with the increase of the frequency detuning of the incident light, the critical power of the control light will rise, while the corresponding critical time will be shortened. It is also revealed that under the same conditions, the critical total power of the multiple-beam control light is less than the one of the single-beam control light. The theoretical predictions show perfect agreement with the simulation results.

The sirtuin proteins are nicotinamide adenine dinucleotide dependent deacetylases and adenosine diphosphate (ADP)-ribosyl transferases associated with metabolic balance and lifespan extension. Sirtuin 1 (SIRT1) and sirtuin 4 (SIRT4) have been reported to regulate insulin secretion, but their association with the development of insulin resistance and nonalcoholic fatty liver disease remain undefined. The aim of this study was to determine the expression of SIRT1 and SIRT4 in the liver and pancreas of rats fed with different diets and analyze the association of these proteins with insulin resistance and nonalcoholic fatty liver disease. Male Sprague-Dawley rats were randomly divided into the following 4 diet treatment groups: normal control (NC), calorie restriction (CR), high-fat (HFa), and high-fructose (HFr), and these groups were maintained for 12 weeks. Blood biochemical analysis and histopathology indicated that HFa and HFr groups were insulin resistant and developed nonalcoholic fatty livers. SIRT1 was present in the nucleus and cytoplasm of the pancreatic beta-cells, while SIRT4 was located in the cytoplasm. Treatment with the CR diet increased the expression of SIRT1 in both the pancreas and liver, while treatment with the HFa and HFr diets caused a decrease. SIRT4 was upregulated in the liver of rats treated with the HFa diet, but did not change with the CR diet treatment. These data suggest that SIRT1 and SIRT4 were both involved in the development of insulin resistance and nonalcoholic fatty liver disease.

Objective: To further understand the pathogenesis of pneumococcal meningitis, and provide some target candidates for the development of drugs., Methods: This study was performed at the Department of Laboratory Medicine, Key Laboratory of Diagnostic Medicine (Ministry of Education), Chongqing Medical University, Chongqing, China from March 2006 to December 2007. A promoter-trap library of Streptococcus pneumoniae TIGR4, reported by green fluorescent protein was constructed, and used to infect BALB/c mice (n=15) intranasally, to set up a meningitis model. The control group (n=5) were inoculated with sterile phosphate buffered saline. The bacteria containing the promoter fusions induced only in meningitis brain tissue, not in vitro were screened by differential fluorescence induction. The obtained bacteria were prepared to re-infect the mice and re-screened, as above. The sorted bacteria were spread on trypticase soy agar with 5% sheep blood agar plates containing chloramphenicol (2.5 g/mL), and were used for DNA cloning, sequencing, and bioinformatics analysis., Results: A total of 52 genes were obtained. Bioinformatics analysis revealed that these in vivo induced genes were involved in functions such as, adherence, energy metabolism, nutrient substance transport, transcription regulation, DNA metabolism, as well as, cell wall synthesis. In addition, there were some genes encoding for some hypothetical proteins with unknown, or putative functions., Conclusion: Pneumococcal genes involved in meningitis identified in this study are potential targets to understand the pathogenesis of pneumococcal meningitis.

A wavelength switchable all-fiber comb filter with flat-top spectral response based on a double-loop Mach-Zehnder (M-Z) interferometer is proposed and demonstrated. The proposed flat-top filter consists of a rotatable polarizer and a double-loop M-Z interferometer composed of two fiber couplers with a polarization controller (PC) in the first loop. In the theoretical analysis, when the second coupler of the M-Z interferometer is a non-3dB one, with proper settings of the polarization state of the input light and the PC, the wavelength switchable comb filter with flat-top passband can be obtained. Theoretical prediction was verified by experimental demonstration. The measured 1 dB bandwidth was 0.51 nm with a channel spacing of 0.98 nm, indicating that the flat-top passband of 1 dB bandwidth extends to about 50% of the comb spacing.