Genistein Alleviates Oxidative Stress and Inflammation in the Hypothalamic Paraventricular Nucleus by Activating the Sirt1/Nrf2 Pathway in High Salt-Induced Hypertension.

Hypertension caused by a high-salt (HS) diet is one of the major causes of cardiovascular diseases. Underlining pathology includes oxidative stress and inflammation in the hypothalamic paraventricular nucleus (PVN). This study investigates genistein's (Gen) role in HS-induced hypertension and the underlying molecular mechanism. We placed male Wistar rats on HS (8% NaCl) or normal salt diet (0.3% NaCl). Then, we injected bilateral PVN in rats with Gen, vehicle, or nicotinamide (NAM) for 4 weeks. Tail cuff was used weekly to assess the systolic pressure, diastolic pressure, and mean arterial pressure (MAP). Cardiac hypertrophy was analyzed by heart weight/body weight ratio and wheat germ agglutinin staining. ELISA kits, Western blot, or dihydroethidium staining determined the levels of inflammatory cytokines and oxidative stress markers. Western blot measured protein levels of Sirt1, Ac-FOXO1, Nrf2, NQO-1, HO-1, and gp91phox. Our result showed that PVN infusion of Gen significantly reduced the increase of systolic pressure, diastolic pressure, and MAP induced by an HS diet. Additionally, there was a decrease in cardiac hypertrophy and the levels of inflammatory cytokines in PVN and plasma. Meanwhile, PVN infusion of Gen notably inhibited the levels of oxidized glutathione and superoxide dismutase and improved the glutathione level and total antioxidant capacities and superoxide dismutase activities. It also decreased the level of reactive oxygen species and gp91phox expression in PVN. Furthermore, Gen infusion markedly increases the Sirt1, Nrf2, HO-1, and NQO-1 levels and decreases the Ac-FOXO1 level. However, PVN infusion of NAM could significantly block these changes induced by Gen in HS diet rats. Our results demonstrated that PVN infusion of Gen could inhibit the progression of hypertension induced by an HS diet by activating the Sirt1/Nrf2 pathway.

Fast-response humidity sensor based on laser printing for respiration monitoring.

Respiration monitoring equipment has wide applications in daily health monitoring and modern medical diagnosis. Despite significant progress being made in humidity sensors for respiration monitoring, the fabrication of the humidity sensors with low-cost, simple manufacturing process and easy integration remains a challenge. This work reports a facile and inexpensive laser printing fabrication of PEDOT:PSS micron line as a humidity sensor for respiration monitoring. Laser printing technology can process any material into an arbitrary pattern. The PEDOT:PSS micron line humidity sensor has a fast response-recovery time (0.86 s/0.59 s), demonstrating excellent performance for real-time monitoring of human respiration. Furthermore, the PEDOT:PSS micron line humidity sensor can also monitor the respiration of rats under different physiological conditions along with the drug injection. The PEDOT:PSS micron line humidity sensor features simple manufacturing process with commercial materials, and easy integration with wearable devices. This work paves an important step in real-time monitoring of human health and further physiology and pharmacology study.

Dual-3D Femtosecond Laser Nanofabrication Enables Dynamic Actuation.

Strategies that can make general materials smart are highly desired for developing artificial shape-morphing systems and devices. However, at present, it still lacks universal technologies that enable designable prototyping of deformable 3D micro-nanostructures. Inspired by natural automation systems, for instance, tendrils, leaves, and flowers deform dynamically under external stimuli by varying internal turgor, we report a dual-3D femtosecond laser processing strategy for fabricating smart and deformable 3D microactuators based on general photopolymers. By programming the size and distributions of voxels at the nanoscale, both the 3D profile and the 3D internetwork of a general photopolymer could be tailored in a controlled manner; thus, 3D microstructures encoded with precisely tailored networks could perform predictable deformations under certain stimuli. Using this dual-3D fabrication approach, energetic 3D microactuators, including a smart microflower, a responsive microvale, and an eight-finger microclaw, that permit controllable manipulation have been successfully developed.

Ship-in-a-bottle femtosecond laser integration of optofluidic microlens arrays with center-pass units enabling coupling-free parallel cell counting with a 100% success rate.

Optimal design and fabrication of novel devices for high-performance optofluidic applications is a key issue for the development of advanced lab-on-a-chip systems. Parallel cell counting with a high success rate and simple mode of operation is a challenging goal. Current cell-counting methods, using optical waveguides or flow cytometry, typically require a precise coupling of the probe light and involve complex operations. In the present paper, a novel multifunctional cell counting microdevice is designed. It uses a center-pass optofluidic microlens array (MLA) consisting of seven microlenses and an M-shaped confining wall with 9 µm-diameter apertures. The device can be fabricated in a three-dimensional microchannel by ship-in-a-bottle femtosecond laser integration based on two-photon polymerization with optimized experimental parameters. Each microlens produces approximately the same intensity at the focal positions (within ±5%) under white-light illumination, while the confining wall restricts 6∼8 µm-width cells to passing through the edges of two adjacent microlenses because the aperture opens toward their centers. The device demonstrates coupling-free parallel cell counting with a 100% success rate by monitoring the optical intensity variations at each spot. As a result, this method features both easy operation and high performance. Furthermore, the confining wall can filter deformed cells having 15 µm width.

Monolithic bifocal zone-plate lenses for confocal collimation of laser diodes.

An elliptical monolithic bifocal zone plate as a collimating lens, whose two focal lengths in the orthogonal directions match the different beam waist positions of the fast and slow axes' light from edge-emitting laser diodes, is proposed and experimentally demonstrated by employing femtosecond laser direct writing technology. The high-quality eight-level zone plate exhibits a diffraction efficiency of 92.9%, which is much higher than those ever reported. Shaped by the elliptical lens, the laser diodes' divergence angles are simultaneously reduced from 65° (1134 mrad, fast axis) and 24° (418 mrad, slow axis) to 7.7 and 136.5 mrad, respectively.

Complex three-dimensional polymer-metal core-shell structures towards emission control.

We report the fabrication of three-dimensional periodic metal nickel nanostructures achieved by the combination of femtosecond laser-induced two-photon polymerization and electroless plating technology. We can control the deposition speed of 10 nm per second by adjusting the reaction time. The thermal stability is good under 500 °C for the three-dimensional graphite-lattice polymer structure with 200 nm nickel film. Optical reflectivity and thermal emission measurements under 550 °C showed that the fabricated metallic structure was thermally excited and emitted light at λ = 4.50, 4.95 µm. The emission peak wavelengths agree with the absorption peaks. These data demonstrate that creating metallic photonic crystals by incorporation of metals to laser-fabricated templates is a simple and cost-efficient method. The emitters can work at such low temperatures, which is more important for realistic operation in applications.

Localized flexible integration of high-efficiency surface enhanced Raman scattering (SERS) monitors into microfluidic channels.

We report here a facile approach for flexible integration of high efficiency surface enhanced Raman scattering (SERS) monitors in a continuous microfluidic channel. In our work, femtosecond laser direct writing was adopted for highly localizable and controllable fabrication of the SERS monitor through a multi-photon absorption (MPA) induced photoreduction of silver salt solution. The silver substrate could be shaped into designed patterns, and could be precisely located at the desired position of the microchannel bed, giving the feasibility for real-time detection during reactions. SEM and TEM images show that the silver substrates were composed of crystallized silver nanoplates with an average thickness of 50 nm. AFM results reveal that the substrates were about 600 nm in height and the surface was very rough. As representative tests for SERS detection, p-aminothiophenol (p-ATP) and flavin adenine dinucleotide (FAD) were chosen as probing molecules for microfluidic analysis at visible light (514.5 nm) excitation, exhibiting an enhancement factor of ~10(8). In addition, the combination of the SERS substrate with the microfluidic channel allows detection of inactive analytes through in situ microfluidic reactions.

One-step preparation of regular micropearl arrays for two-direction controllable anisotropic wetting.

In this paper, one simple method to control two-direction anisotropic wetting by regular micropearl arrays was demonstrated. Various micropearl arrays with large area were rapidly fabricated by a kind of improved laser interference lithography. Specially, we found that the parallel contact angle (CA) theta(2) decreased from 93 degrees to 67 degrees as the intensity ratio of four laser beams increased from 2:1 to 30:1, while the perpendicular CA theta(1) determined by the thickness of the resin remained constant. This was interpreted as the decrease of height variations Delta h from 1100 to 200 nm along the parallel direction caused by the increase of the intensity ratio. According to this rule, both theta(1) and theta(2) could be simultaneously controlled by adjusting the height variation Delta h and the resin thickness. Moreover, by combining appropriate design and low surface energy modification, a natural anisotropic rice leaf exhibiting CAs of 146 degrees +/- 2 degrees/153 degrees +/- 3 degrees could be mimicked by our anisotropic biosurface with the CAs 145 degrees +/- 1 degrees/150 degrees +/- 2 degrees. We believe that these controlled anisotropic biosurfaces will be helpful for designing smart, fluid-controllable interfaces that may be applied in novel microfluidic devices, evaporation-driven micro/nanostructures, and liquid microdroplet directional transfer.

Embellishment of microfluidic devices via femtosecond laser micronanofabrication for chip functionalization.

This paper demonstrates the embellishment of existing microfluidic devices with integrated three dimensional (3D) micronanostructures via femtosecond laser micronanofabrication, which, for the first time, proves two-photon photopolymerization (TPP) to be a powerful technology for chip functionalization. As representative examples, microsieves with various pore shape and adjustable pore size were successfully fabricated inside a conventional glass-based microfluidic channel prepared by wet etching for microparticle separation. Moreover, a fish scale like microfilter was also fabricated and appointed as a one-way valve, which showed excellent performance as we expected. These results indicate that such embellishment of microfluidic devices is simple, low cost, flexible and easy to access. We believe that, combined with TPP, the application of lab-on-chip devices would be further extended.

[Abnormal expression of beta-catenin and E-cadherin in Her2-positive breast cancer and its implications].

OBJECTIVE: To investigate the relationship between positive expression of Her2 and abnormal expressions of beta-catenin and E-cadherin and its implications. METHODS: Immunohistochemistry was used to detect the expressions of Her2, beta-catenin and E-cadherin in 147 samples of human breast carcinoma. The expressions of beta-catenin and E-cadherin were also detected in 19 tissues adjacent to the carcinoma and 17 benign breast lesions as controls. RESULTS: In breast carcinoma, positive Her2 expression was associated with lymph node metastasis, advanced clinical stage and negative expression of ER and PR (P<0.05). Abnormal beta-catenin expression was associated with positive lymph node status and high histological grade (P<0.01). Abnormality of E-cadherin expression was related to lymph node metastasis and advanced clinical stage (P<0.05). Abnormal beta-catenin expression was directly correlated with abnormal E-cadherin expression (P<0.01). Her2 positivity showed a direct correlation to abnormal beta-catenin expression (P<0.01), and they cooperated in promoting axillary lymph node metastasis in human breast carcinoma (P<0.01). CONCLUSION: A direct correlation between positive Her2 expression and abnormal beta-catenin expression exists in human breast carcinoma, and positive Her2 expression may have functional interactions with abnormal activation of Wnt/beta-catenin signaling pathway.

Femtosecond laser rapid prototyping of nanoshells and suspending components towards microfluidic devices.

Microfluidic researches are now resorting to advanced micro-nanoprocessing technologies for production of more functional "lab-on-a-chip" systems. However, two-photon polymerization (TPP), a powerful designable micro-nanofabrication approach, has not been put to use on the exciting field, largely due to the difficulties in forming buried channels. Here, we solve the problem by TPP prototyping of nanoshells, for which the usage of the negative tone resin SU-8 is found critical. The fabrication efficiency improved by orders of magnitude, together with the prospect of integration of movable micro-mechanical and optical components into the chip would make TPP a promising enabling tool for the micro-analytical systems. Finally, a 25 microm length functional microvalve in a microfluidic channel was rapidly realized and its "ON" and "OFF" states were tested.

Remote manipulation of micronanomachines containing magnetic nanoparticles.

We report remote manipulation of micronanomachines containing magnetic nanoparticles. Surface-modified Fe(3)O(4) nanocrystals were synthesized as doping agents of the photopolymerizable resin, which was pinpoint written by femtosecond laser-induced two-photon photopolymerization to create microsprings. Owing to the nature of superparamagnetism of Fe(3)O(4) nanoparticles, force exerted to the microsprings relies sensitively on the field gradient of the external ferromagnet, and various motions like elongation, bending, and swing are achieved in a well-controllable remote manner. As a noncontact, sensitive, easy, and environmentally friendly approach, the magnetic driving of micronanomachines may play an important role for nano and biological applications.

High efficiency multilevel phase-type fractal zone plates.

Three kinds of high efficiency phase-type fractal zone plates were rapidly (in tens of minutes) fabricated by femtosecond laser two-photon photopolymerization. Their theoretical maximal diffractive efficiencies of 24.5%, 12.52%, and 18.76% were predicted both by numerical simulation and analytical deduction and were verified by the measured values of 20.5%, 9.1%, and 13%, respectively. The characteristic of multifoci and the improved imaging ability for phase-type fractal lens was also demonstrated. Moreover, to further enhance the diffractive efficiency, a four-level fractal phase lens, whose diffraction efficiency reached as high as 37.6%, was proposed and realized.

Dammann gratings as integratable micro-optical elements created by laser micronanofabrication via two-photon photopolymerization.

Dammann gratings, as beam splitters and coherent signal generators, were produced in a short fabricating cycle by femtosecond laser fabrication via two-photon photopolymerization. These holograms that each generated 2x2, 3x3, 4x4, 5x5, and 6x6 spot sources in the fan-out demonstrated diffraction efficiency of 36%, 25%, 29%, 52%, and 49%, respectively, comparable with the theoretical values. This work shows the promising prospect of femtosecond laser fabrication in compatibly manufacturing various micro-optical devices including Dammann gratings and their integrated systems.