Wideband chaotic tri-mode microlasers with optical feedback.

A tri-mode micro-square laser under optical feedback is proposed and demonstrated to generate chaos with the broadband flat microwave spectrum. By adjusting lasing mode intensities, frequency intervals, and optical feedback strength, we can enhance the chaotic bandwidth significantly. The existence of two mode-beating peaks makes the flat bandwidth much larger than the relaxation oscillation frequency. Effective bandwidth of 35.3 GHz is experimentally achieved with the flatness of 8.3 dB from the chaotic output spectrum of the tri-mode mode laser under optical feedback.

Optical frequency comb and picosecond pulse generation based on a directly modulated microcavity laser.

Optical frequency comb (OFC) and picosecond pulse generation are demonstrated experimentally based on a directly modulated AlGaInAs/InP square microcavity laser. With the merit of a high electro-optics modulation response of the microcavity laser, power-efficient OFCs with good flatness are produced. Ten 8-GHz-spaced optical tones with power fluctuation less than 3 dB are obtained based on the laser modulated by a sinusoidal signal. Moreover, the comb line number is enhanced to 20 by eliminating the nonlinear dynamics through optical injection locking. Owing to the high coherence of the OFC originating from the directly modulated microcavity laser, a 6.8 ps transform-limited pulse is obtained through dispersion compensation. The optical pulse is further compressed to 1.3 ps through the self-phase modulation effect in high nonlinear fiber.

Lethal giant larvae 1 inhibits smooth muscle calcification via high mobility group box 1.

Vascular calcification is a pathological process closely related to atherosclerosis, diabetic vascular diseases, vascular injury, hypertension, chronic kidney disease and aging. Lethal giant larvae 1 (LGL1) is known as a key regulator of cell polarity and plays an important role in tumorigenesis. However, whether LGL1 regulates vascular calcification remains unclear. In this study, we generated smooth muscle-specific LGL1 knockout (LGL1SMKO) mice by cross-breeding LGL1flox/flox mice with α-SMA-Cre mice. LGL1 level was significantly decreased during calcifying conditions. Overexpression of LGL1 restrained high phosphate-induced calcification in vascular smooth muscle cells (VSMCs). Mechanically, LGL1 could bind with high mobility group box 1 (HMGB1) and promote its degradation via the lysosomal pathway, thereby inhibiting calcification. Smooth muscle-specific deletion of LGL1 increased HMGB1 level and aggravated vitamin D3-induced vascular calcification, which was attenuated by an HMGB1 inhibitor. LGL1 may inhibit vascular calcification by preventing osteogenic differentiation via promoting HMGB1 degradation.

Quantitative measurement of hydrogen isotopes in titanium using laser-induced breakdown spectroscopy.

Laser-induced breakdown spectroscopy (LIBS) has been considered a promising technology for nuclear safeguard inspection, especially for isotope content ratio determination, since it can be easily designed for portable, fast, and in situ measurement. However, it was a challenge to determine hydrogen isotopes in metal samples due to the unfavorable spectral interference, the poor calibration of the hydrogen content, and the small difference between the atomic emission intensity of hydrogen isotopes at around 656.28 nm. This paper presents the determination of hydrogen isotope contents ratio using LIBS under partially baseline-resolved conditions. The results show that by introducing a proper buffer atmosphere for the LIBS measurement, the resolution of the hydrogen and deuterium emissions could be improved, but still not enabled, by a baseline resolution with a moderate resolution spectrometer. However, with the method of integral intensity correction, the accurate quantitative measurement of hydrogen and deuterium contents in a metal matrix could be achieved. This work provided the possibilities for the further development of LIBS in hydrogen isotopes in in situ measurement for nuclear safeguards.

Wideband multiwavelength Brillouin fiber laser based on dual-mode AlGaInAs/InP microcavity lasers.

A multiwavelength Brillouin fiber laser (BFL) is demonstrated using a 1.55-µm AlGaInAs/InP microcavity laser as a seed source. The combination of a nonlinear fiber cavity and a feedback loop leads to multiwavelength generation with a channel spacing of double-Brillouin-frequency assisted by cavity-enhanced four-wave mixing. The amplified output of a dual-mode lasing square microcavity laser with a wavelength interval of 1.5 nm is applied as the pump source for the broadband multiwavelength generation. A wideband multiwavelength BFL covering from 1490 nm to 1590 nm is successfully generated at an optimized pump power of 25 dBm and a feedback power of -17.2dBm. The power stability of 0.82 dB over a 60 min duration of the multiwavelength BFL can satisfy the demands for the optical fiber sensing and microwave photonic systems.

Smooth muscle-specific LKB1 deletion exaggerates angiotensin II-induced abdominal aortic aneurysm in mice.

Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease without an effective pharmaceutical treatment. Liver kinase B1 (LKB1), a tumor suppressor, is a central regulator of cell polarity and energy homeostasis. However, the role of LKB1 in the development of AAA has not been explored. In this study, mice with knockout of smooth muscle-specific LKB1 (LKB1SMKO) were generated by cross-breeding LKB1flox/flox mice with SM22-CreERT2 transgenic mice and induced in adult mice by tamoxifen treatment. LKB1 deficiency increased the expression of matrix metalloproteinase 2 (MMP-2), which was inhibited by LKB1 overexpression. Mechanistically, LKB1 could bind to the MMP-2 transcription factor, specificity protein 1 (Sp1), thereby reducing the binding of Sp1 to the MMP-2 promoter to inhibit MMP-2 expression. LKB1 expression was significantly reduced in abdominal aortas of the mouse AAA model. Moreover, smooth muscle-specific LKB1 deletion exaggerated angiotensin II-induced AAA formation accompanied by increased AAA incidence and aortic expansion. Finally, LKB1 level was significantly lower and MMP-2 level higher in human AAA samples than adjacent nonaneurysmal aortic sections. Thus, these results suggest that LKB1 may play a protective role in AAA formation by inhibiting MMP-2 expression and could be a potential therapeutic target for AAA disease.

Sequential Delivery of Dual Growth Factors from Injectable Chitosan-Based Composite Hydrogels.

Local administration of platelet-derived growth factor-BB (PGDF-BB) and bone morphogenetic protein-2 (BMP-2) in a sequential release manner could substantially promote bone healing. To achieve this goal, a delivery system that could sustain the release of PGDF-BB and BMP-2 by way of temporal separation was developed. One type of PGDF-BB-encapsulated alginate microsphere and another type of BMP-2-encapsulated microsphere with a core-shell structure were respectively produced using emulsification methods. These two types of microspheres were then embedded into chitosan/glycerophosphate hydrogel for constructing composite gels. Some of them were found to be injectable at ambient temperature and had thermo-sensitive features near physiological temperature and pH. The optimally formulated composite gels showed the ability to control the release of PGDF-BB and BMP-2 in a sequential fashion in which PDGF-BB was released earlier than BMP-2. In vitro release patterns indicated that the release rates could be significantly regulated by varying the embedded amount of the factor-encapsulated microspheres, which can in turn mediate the temporal separation release interval between PGDF-BB and BMP-2. The released PDGF-BB and BMP-2 were detected to be bioactive based on their respective effects on Balb/c 3T3 and C2C12 cells. These results suggest that the presently developed composite gels have the potential for bone repair by synergistically utilizing the early chemotactic effect of PDGF-BB and the subsequent osteogenic and angiogenic functions of PDGF-BB and BMP-2.

Low-phase-noise microwave generation using dual-mode microsquare laser phase locking by modulated sidebands.

An effective method for millimeter-wave (mmW) carrier generation from a dual-transverse-mode microsquare laser is experimentally demonstrated. By directly modulating the dual-mode microsquare laser at 6.7 GHz, multiple sidebands are generated due to enhanced modulation nonlinearity, and the lasing modes with an interval of 40 GHz are phase-locked. MmW carriers up to 47 GHz, corresponding to seven times that of the modulation frequency, are achieved with a linewidth below 10 Hz. The single-sideband phase noises of the signals keep the same level after transmission over 2.5 km of optical fiber.

Protective effect of Flos puerariae extract following acute alcohol intoxication in mice.

BACKGROUND: The effect of Flos Puerariae extract (FPE) on alcohol metabolism, hepatic injury, and memory impairment was assessed following acute ethanol (EtOH) intoxication in mice. METHODS: The model of acute EtOH intoxication was established by intragastric administration with 8 g/kg EtOH in mice. FPE was orally administrated (gavage) once a day for 7 consecutive days. Mice were randomly divided into 4 groups: control group, model group, and FPE groups (100, 200 mg/kg). Alcohol tolerance and intoxication time, blood alcohol concentration, the activities of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) in liver, aspartate amino transferase (AST) and alanine amino transferase (ALT) in serum, superoxide dismutase (SOD), glutathione peroxidase (GSH-px), catalase and the formation of malondialdehyde (MDA) in both liver and brain, as well as memory ability were determined after acute alcohol exposure. RESULTS: Compared with model group, pretreatment with FPE significantly prolonged alcohol tolerance time and shortened intoxication time, which is accompanied by decreased blood alcohol concentration and elevated activities of ADH and ALDH in liver. Moreover, the index of hepatic injury, ALT, and AST activities in serum was markedly decreased by pretreatment with FPE. Additionally, decreased MDA level, enhanced GSH-px and catalase activities in liver, as well as enhanced SOD and catalase activities in brain were found in FPE pretreated mice after acute exposure to EtOH. Furthermore, FPE pretreated mice showed markedly relieved memory disruption following acute EtOH intoxication. CONCLUSIONS: This study suggests that FPE pretreatment could enhance alcohol metabolism, prevent hepatic injury, and relieve memory impairment after acute alcohol intoxication and that this effect is likely related to its modulation on the alcohol metabolizing and antioxidant enzymes.

Prokineticin 2 potentiates acid-sensing ion channel activity in rat dorsal root ganglion neurons.

BACKGROUND: Prokineticin 2 (PK2) is a secreted protein and causes potent hyperalgesia in vivo, and is therefore considered to be a new pronociceptive mediator. However, the molecular targets responsible for the pronociceptive effects of PK2 are still poorly understood. Here, we have found that PK2 potentiates the activity of acid-sensing ion channels in the primary sensory neurons. METHODS: In the present study, experiments were performed on neurons freshly isolated from rat dorsal root ganglion by using whole-cell patch clamp and voltage-clamp recording techniques. RESULTS: PK2 dose-dependently enhanced proton-gated currents with an EC50 of 0.22 ± 0.06 nM. PK2 shifted the proton concentration-response curve upwards, with a 1.81 ± 0.11 fold increase of the maximal current response. PK2 enhancing effect on proton-gated currents was completely blocked by PK2 receptor antagonist. The potentiation was also abolished by intracellular dialysis of GF109203X, a protein kinase C inhibitor, or FSC-231, a protein interacting with C-kinase 1 inhibitor. Moreover, PK2 enhanced the acid-evoked membrane excitability of rat dorsal root ganglion neurons and caused a significant increase in the amplitude of the depolarization and the number of spikes induced by acid stimuli. Finally, PK2 exacerbated nociceptive responses to the injection of acetic acid in rats. CONCLUSION: These results suggest that PK2 increases the activity of acid-sensing ion channels via the PK2 receptor and protein kinase C-dependent signal pathways in rat primary sensory neurons. Our findings support that PK2 is a proalgesic factor and its signaling likely contributes to acidosis-evoked pain by sensitizing acid-sensing ion channels.

Template-free fabrication of Bi2O3 and (BiO)2CO3 nanotubes and their application in water treatment.

Uniform bismuth oxide (Bi(2)O(3)) and bismuth subcarbonate ((BiO)(2)CO(3)) nanotubes were successfully synthesized by a facile solvothermal method without the need for any surfactants or templates. The synergistic effect of ethylene glycol (EG) and urea played a critical role in the formation of the tubular nanostructures. These Bi(2)O(3) and (BiO)(2)CO(3) nanotubes exhibited excellent Cr(VI)-removal capacity. Bi(2)O(3) nanotubes, with a maximum Cr(VI)-removal capacity of 79 mg g(-1), possessed high removal ability in a wide range of pH values (3-11). Moreover, Bi(2)O(3) and (BiO)(2)CO(3) nanotubes also displayed highly efficient photocatalytic activity for the degradation of RhB under visible-light irradiation. This work not only demonstrates a new and facile route for the fabrication of Bi(2)O(3) and (BiO)(2)CO(3) nanotubes, but also provides new promising adsorbents for the removal of heavy-metal ions and potential photocatalysts for environmental remediation.

Strong and Elastic Chitosan/Silk Fibroin Hydrogels Incorporated with Growth-Factor-Loaded Microspheres for Cartilage Tissue Engineering.

An emulsification method was developed for fabricating core-shell microspheres with a thick shell layer. Kartogenin (KGN) and platelet-derived growth factor BB (PDGF-BB) were respectively loaded into the core portion and the shell layer of the microspheres with high loading efficiency. The optimally built microspheres were combined with chitosan (CH) and silk fibroin (SF) to construct a new type of composite hydrogel with enhanced strength and elasticity, using genipin or/and tyrosinase as crosslinkers for the intended use in cartilage tissue engineering. The composite hydrogels were found to be thermo-responsive at physiological temperature and pH with well-defined injectability. Rheological measurements revealed that they had an elastic modulus higher than 6 kPa with a high ratio of elastic modulus to viscous modulus, indicative of their mechanically strong features. Compressive measurements demonstrated that they possessed well-defined elasticity. In addition, some gels had the ability to administer the temporal separation release of PDGF-BB and KGN in an approximately linear manner for several weeks. The released PDGF-BB was found to be bioactive based on its effects on Balb/c 3T3 cells. The composite gels supported the growth of seeded chondrocytes while preserving their phenotype. The results suggest that these composite gels have the potential for endogenous cartilage repair.

Strong and Elastic Hydrogels from Dual-Crosslinked Composites Composed of Glycol Chitosan and Amino-Functionalized Bioactive Glass Nanoparticles.

Mesoporous bioactive glass (BG) nanoparticles (NPs) with a high specific surface area were prepared. The surfaces of BG NPs were further modified using an amino-containing compound or synthesized precursors to produce three kinds of amino-functionalized bioactive glass (ABG) NPs via devised synthetic routes. The achieved ABG NPs possessed various spacer lengths with free amino groups anchored at the end of the spacer. These ABG NPs were then combined with glycol chitosan (GCH) to construct single- or dual-crosslinked ABG/GCH composite hydrogels using genipin (GN) alone as a single crosslinker or a combination of GN and poly(ethylene glycol) diglycidyl ether (PEGDE) as dual crosslinkers. The spacer length of ABG NPs was found to impose significant effects on the strength and elasticity of GN-crosslinked ABG/GCH hydrogels. After being dually crosslinked with GN and PEGDE, the elastic modulus of some dual-crosslinked ABG/GCH hydrogels reached around 6.9 kPa or higher with their yielding strains larger than 60%, indicative of their strong and elastic features. The optimally achieved ABG/GCH hydrogels were injectable with tunable gelation time, and also able to support the growth of seeded MC3T3-E1 cells and specific matrix deposition. These results suggest that the dual-crosslinked ABG/GCH hydrogels have the potential for some applications in tissue engineering.

Activation of AMP-activated protein kinase alpha1 alleviates endothelial cell apoptosis by increasing the expression of anti-apoptotic proteins Bcl-2 and survivin.

Accumulating evidence suggests that AMP-activated protein kinase (AMPK) activation exerts anti-apoptotic effects in multiple types of cells. However, the underlying mechanisms remain poorly defined. The aim of the present study was to determine how AMPK suppresses apoptosis in endothelial cells exposed to hypoxia and glucose deprivation (OGD). AMPK activity, NF-kappaB activation, and endothelial cell apoptosis were assayed in cultured endothelial cells and mouse common carotid artery with or without OGD treatment. OGD markedly activated AMPK as early as 30 min, and AMPK activity reached maximal at 2 h of OGD. Endothelial apoptosis was not detected until 2 h of OGD but became markedly elevated at 6 h of OGD treatment. Furthermore, AMPK inhibition by Compound C or overexpression of dominant negative AMPK (AMPK-DN) exacerbated, whereas AMPK activation by pharmacologic (aminoimidazole carboxamide ribonucleotide (AICAR)) or genetic means (overexpression of constitutively active AMPK) suppressed endothelial cell apoptosis caused by OGD. Concomitantly, AMPK activation increased the expression of both Bcl-2 and Survivin, two potent anti-apoptotic proteins. Furthermore, AMPK activation significantly enhanced IkappaBalpha kinase activation, NF-kappaB nuclear translocation, and DNA binding activity of NF-kappaB. Consistently, selective inhibition of NF-kappaB, which abolished OGD-enhanced expression of Bcl-2 and Survivin, accentuated endothelial apoptosis caused by OGD. Finally, we found that genetic deletion of the AMPKalpha1, but not AMPKalpha2, suppressed OGD-enhanced NF-kappaB activation, the expression of Bcl-2 and Survivin, and endothelial apoptosis. Overall, our results suggest that AMPKalpha1, but not AMPKalpha2 activation, promotes cell survival by increasing NF-kappaB-mediated expression of anti-apoptotic proteins (Bcl-2 and Survivin) and intracellular ATP contents.

Liver kinase B1 inhibits smooth muscle calcification via high mobility group box 1.

Vascular calcification is a common pathological feature of atherosclerosis, chronic kidney disease, vascular injury, and aging. Liver kinase B1 (LKB1) plays pivotal roles in cellular processes such as apoptosis, metabolism, and cell cycle regulation. In addition, growing evidence has indicated that LKB1 functions as a tumor suppressor gene. However, its role in vascular calcification has not been reported. LKB1flox/flox mice were hybridized with SM22-CreERT2 transgenic mice and adult mice received tamoxifen to obtain smooth muscle-specific LKB1-knockout (LKB1SMKO) mice. LKB1 expression was decreased under calcifying conditions, and LKB1 overexpression had a protective effect on vascular calcification. However, high mobility group box 1 (HMGB1) overexpression partially counteracted the promotion of vascular calcification induced by LKB1 overexpression. Mechanically, LKB1 could bind to HMGB1 to promote HMGB1 degradation. Furthermore, LKB1SMKO mice showed intensified vascular calcification, which was alleviated by treatment with the HMGB1 inhibitor glycyrrhizic acid. Based on our results, LKB1 may inhibit vascular calcification via inhibiting HMGB1 expression.

Activating Titanium Metal with H2 Plasma for the Hydrogen Evolution Reaction.

Developing a high-performance nonprecious metal electrocatalyst for water splitting is a strong demand for the large-scale application of electrochemical H2 production. In this work, we design a facile and scalable strategy to activate titanium metal for the hydrogen evolution reaction (HER) in alkaline media through incorporating hydrogen into the α-Ti crystal lattice by H2 plasma bombardment. Benefiting from the accelerated charge transfer and enlarged electrochemical surface area after H2 plasma treatment, the H-incorporated Ti shows remarkably enhanced HER activity with a much lower overpotential at -10 mA cm-2 by 276 mV when compared to the pristine Ti. It is revealed that the retention of the incorporated H(D) atoms in the Ti crystal lattice during HER accounts for the durable feature of the catalyst. Density functional theory calculations demonstrate the effectiveness of hydrogen incorporation in tuning the adsorption energy of reaction species via charge redistribution. Our work offers a novel route to activate titanium or other metals by H incorporation through a controllable H2 plasma treatment to tune the electronic structure for water splitting reactions.

Neuroprotection by baicalein in ischemic brain injury involves PTEN/AKT pathway.

Recently more evidences support baicalein (Bai) is neuroprotective in models of ischemic stroke. This study was conducted to determine the molecular mechanisms involved in this effect. Either permanent or transient (2 h) middle cerebral artery occlusion (MCAO) was induced in rats in this study. Permanent MCAO led to larger infarct volumes in contrast to transient MCAO. Only in transient MCAO, Bai administration significantly reduced infarct size. Baicalein also markedly reduced apoptosis in the penumbra of transient MCAO rats. Additionally, oxygen and glucose deprivation (OGD) was used to mimic ischemic insult in primary cultured cortical neurons. A rapid increase in the intracellular reactive oxygen species level and nitrotyrosine formation induced by OGD was counteracted by Bai, which is parallel with attenuated cell injury. The reduction of phosphorylation Akt and glycogen synthase kinase-3beta (GSK3beta) induced by OGD was restored by Bai, which was associated with preserved levels of phosphorylation of PTEN, the phophatase that negatively regulates Akt. As a consequence, Bcl-2/Bcl-xL-associated death protein phosphorylation was increased and the protein level of Bcl-2 in motochondria was maintained, which subsequently antagonize cytochrome c released in cytosol. LY294002 blocked the increase in phospho-AKT evoked by Bai and abolished the associated protective effect. Together, these findings provide evidence that Bai protects neurons against ischemia injury and this neuroprotective effect involves PI3K/Akt and PTEN pathway.

Thromboxane receptor activates the AMP-activated protein kinase in vascular smooth muscle cells via hydrogen peroxide.

Thromboxane A2 receptor (TPr) stimulation induces cellular hypertrophy in vascular smooth muscle cells (VSMCs); however, regulation of VSMC hypertrophy remains poorly understood. Here we show that TPr stimulation activates AMP-activated kinase (AMPK), which in turn limits TPr-induced protein synthesis in VSMCs. Exposure of cultured VSMCs to either TPr agonists, IBOP and U46619, or exogenous hydrogen peroxide (H2O2) caused time- and dose-dependent AMPK activation, as evidenced by increased phosphorylation of both AMPK-Thr172 and acetyl-coenzyme A carboxylase-Ser79, a downstream enzyme of AMPK, whereas SQ29548, a selective TPr antagonist, significantly attenuated TPr-enhanced AMPK activation. In parallel, both IBOP and U46619 significantly increased the production of reactive oxygen species such as H2O2. Furthermore, adenoviral overexpression of catalase (an H2O2 scavenger) abolished, whereas superoxide dismutase (which catalyzes H2O2 formation) enhanced, IBOP-induced AMPK activation, suggesting that TPr-activated AMPK was mediated by H2O2. Consistently, exposure of VSMCs to either TPr agonists or exogenous H2O2 dose-dependently increased the phosphorylation of LKB1 (at serines 428 and 307), an AMPK kinase, as well as coimmunoprecipitation of AMPK with LKB1. In addition, direct mutagenesis of either Ser428 or Ser307 of LKB1 into alanine, like the kinase-dead LKB1 mutant, abolished both TPr-stimulated AMPK activation and coimmunoprecipitation. Finally, genetic inhibition of AMPK significantly accentuated IBOP-enhanced protein synthesis, whereas adenoviral overexpression of constitutively active AMPK abolished IBOP-enhance protein synthesis in VSMCs. We conclude that TPr stimulation triggers reactive oxygen species-mediated LKB1-dependent AMPK activation, which in return inhibits cellular protein synthesis in VSMCs.