Sildenafil increases AAV9 transduction after a systemic administration and enhances AAV9-dystrophin therapeutic effect in mdx mice.

Adeno-associated virus (AAV) vectors have been successfully used to deliver genes for treating rare diseases. However, the systemic administration of high AAV vector doses triggers several adverse effects, including immune response, the asymptomatic elevation of liver transaminase levels, and complement activation. Thus, improving AAV transduction and reducing AAV dosage for treatment is necessary. Recently, we found that a phosphodiesterase-5 inhibitor significantly promoted AAV9 transduction in vitro by regulating the caveolae and macropinocytosis pathways. When AAV9-Gaussian luciferase (AAV9-Gluc) and AAV9-green fluorescent protein (AAV9-GFP) were injected intravenously into mice pre-treated with sildenafil, the expressions of Gluc in the plasma and GFP in muscle tissues significantly increased (P < 0.05). Sildenafil also improved Evans blue permeation in tissues. Additionally, we found that sildenafil promoted Treg proliferation, inhibited B-cell activation, and decreased anti-AAV9 IgG levels (P < 0.05). Furthermore, sildenafil significantly promoted Duchenne muscular dystrophy gene therapy efficacy using AAV9 in mdx mice; it increased micro-dystrophin gene expression, forelimb grip strength, and time spent on the rotarod test, decreased serum creatine kinase levels, and ameliorated histopathology by improving muscle cell morphology and reducing fibrosis (P < 0.05). These results show that sildenafil significantly improved AAV transduction, suppressed the levels of anti-AAV9 IgG, and enhanced the efficacy of gene therapy.

In situ SERS detection of quinolone antibiotic residues in a water environment based on optofluidic in-fiber integrated Ag nanoparticles.

In this paper, we present a microstructured optofluidic in-fiber Raman sensor for the detection of quinolone antibiotic residue in a water environment based on Ag surface-enhanced Raman scattering (SERS) substrate grown on the surface of the suspended core of micro-hollow optical fiber (MHF). Here, MHF has a special structure with a suspended core and a microchannel inside, which can become a natural in-fiber optofluidic device. Meanwhile, the self-assembled Ag SERS substrate can be grown on the suspended core's surface through chemical bonds, forming a microstructured optofluidic device with a Raman enhancement effect. Therefore, it can effectively detect the Raman signal of unlabeled trace quinolone antibiotic residue (ciprofloxacin and norfloxacin) inside the optical fiber. The results show that the ciprofloxacin and norfloxacin detection limits (LOD) are 10-10M and 10-11M, respectively. Compared with the maximum residue limit (3.01×10-7mol/L) stipulated by the European Union, the results are much lower, and an ideal quantitative relationship can be obtained within the detection range. Significantly, this study provides an in-fiber microstructured optofluidic Raman sensor for the label-free detection of quinolone antibiotic residue, which will have good development prospects in the field of antibiotic water pollution environmental detection.

On-line SERS detection of bilirubin based on the optofluidic in-fiber integrated GO/Ag NPs for rapid diagnosis of jaundice.

In this paper, we propose a self-assembled graphene oxide (GO)/Ag NPs SERS Raman sensor based on a novel type of optofluidic MHF as a point-of-care testing (POCT) device. This device is used to diagnose jaundice and its related diseases through on-line detection of free bilirubin content in human serum. This optofluidic Raman sensor is composed of a microstructured hollow fiber (MHF) with a microstructured channel and a suspended core, which allows the sample solution to flow in the channel while interacting with the strong evanescent field on the suspended core. Here, the suspended core was modified by a GO/Ag NPs SERS substrate. When the sample flows through the channel, and interacts with the strong evanescent field generated by the suspended core, the on-line SERS signal is generated and can be coupled back to the suspended core to be detected. In addition, both the electrostatic interaction and interference between GO/Ag NPs with the target enriched bilirubin. The results show that the detection concentration range of bilirubin aqueous, bilirubin in albumin and bilirubin in human blood are all in the range of 2 µM-100 µM, and all have a good linear response. The limit of detection reaches the order of 10-6 M. This rapid, sensitive and label-free SERS Raman sensor of free bilirubin in blood can detect excessive levels of bilirubin in the actual blood environment of the human body, providing a broad prospect for clinically accurate diagnosis of jaundice and related diseases.

All-fiber bidirectional optical modulator derives from the microfiber coated with ITO electrode.

A cheap, compact, and simply prepared all-fiber bidirectional optical modulator based on the Pockels effect of water and the band population effect was first, to the best of our knowledge, proposed and demonstrated. The transparent conductive oxide indium-tin-oxide (ITO) was coated on the surface of a nonadiabatic microfiber and first used as a modulating electrode on the microfiber. The device was realized by just submerging the microfiber in water. With supplying an electric field perpendicular to the interface between the microfiber and water, the refractive index was modulated in the electric double layer near the tapered region of the microfiber, under the Pockels effect of water. Subsequently, the interference spectrum was modulated. Meanwhile, the intensity of the light was modulated due to the band population effect in the space-charge layer. In this Letter, the proposed all-fiber optical modulator can realize simultaneous bidirectional modulation of the phase and intensity of output light. Experimentally, the maximum phase shift and the extinction ratio were 4.38 nm and 4.87 dB at 1550 nm, respectively. Significantly, the work used the Pockels effect of water and the band population effect to realize an all-fiber optical modulator, showing great potential in the optical phase modulators, optical switches, and electric field sensors.

In-fiber optofluidic online SERS detection of trace uremia toxin.

In this Letter, we propose a microstructured in-fiber optofluidic surface-enhanced Raman spectroscopy (SERS) sensor for the initial inspection of uremia through the detection of unlabeled urea and creatinine. As a natural microfluidic device, microstructured hollow fiber has a special structure inside. Through chemical bonds, the SERS substrate can be modified and grown on the surface of the suspended core. Here, the silver nanoparticles (Ag NPs) are embedded on the poly diallyl dimethyl ammonium chloride-modified graphene oxide sheet to achieve the self-assembled SERS substrate. The reduced distance between Ag NPs can increase the strong hot spots that generate enhanced Raman signals. Therefore, it can effectively detect the Raman signal of unlabeled trace uremic toxin analytes (urea, creatinine) inside the optical fiber. The results show that under simulated biophysical conditions, the limit detection (LOD) for urea is 10-4M and the linearity is good, especially at the clinical conventional concentration range (2.5-6.5×10-3M). In addition, the online Raman detection of creatinine aqueous solution LOD is 10-6M, which also has good linearity. Significantly, this Letter provides a microstructured optofluidic in-fiber Raman sensor for the preliminary detection of uremia, which will have good development prospects in the field of clinical biomedicine.

All-fiber phase modulator and switch based on local surface plasmon resonance effect of the gold nanoparticles embedded in gel membrane.

All-fiber modulators and switches have drawn great interest in the photonics domain, and they are applied in viable photonic and optoelectronic devices. In this work, with the assistance of an agarose membrane, aspherical gold nanoparticles are embedded on the surface of the microfiber treated with the piranha solution. An all-fiber Mach-Zehnder interferometer was used to realize a low-cost, low-loss, and conveniently prepared all-fiber phase modulator. By taking advantage of the local surface plasmon resonance effect of gold nanoparticles embedded in the agarose membrane, under the excitation of near-infrared region light, the gold nanoparticles were excited to change the effective refractive index of one arm of the Mach-Zehnder interferometer. A maximum phase shift of ∼6π at 1550 nm was obtained from the device. In addition, an all-optical switch was achieved with a rising edge time of 47 ms and falling edge time of 14 ms. The proposed all-fiber modulator and switch based on the local surface plasmon resonance effect of gold nanoparticles embedded in agarose membrane will provide great potential in all-optical fiber systems.

Optofluidic in-fiber integrated surface-enhanced Raman spectroscopy detection based on a hollow optical fiber with a suspended core.

In this Letter, we propose, to the best of our knowledge, the first in-fiber optofluidic Raman surface-enhanced Raman spectroscopy (SERS) sensor based on a microstructured hollow fiber (MHF) with a suspended core. Taking advantage of the unique internal structure, we immobilize silver nanoparticles with an SERS effect in the MHF by chemical bonding. The Raman signal of the microfluidic sample is excited by the excitation light in the suspended core through an evanescent field. Then the online SERS signal can be coupled back into the core and detected. To demonstrate the feasibility of the device, rhodamine 6G is chosen as the analyte, and high-quality SERS spectra are detected with the limit of detection of 1×10-14 M. Furthermore, an online optofluidic test is conducted on ceftriaxone (C18H18N8O7S3) to examine its capabilities in antibiotic sensing. The results show that the LOD of the samples is 10-6 M. Significantly, this Letter provides an integrated optofluidic in-fiber SERS sensor with a microchannel that can be integrated with chip devices without spatial optical coupling, which has a broad application in medicine and food safety, as well as various aspects of biological in-fiber sensing.