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.

Hydroxyethyl starch-folic acid conjugates stabilized theranostic nanoparticles for cancer therapy.

Small molecular prodrug-based nanomedicines with high drug-loading efficiency and tumor selectivity have attracted great attention for cancer therapy against solid tumors, including triple negative breast cancers (TNBC). However, abnormal tumor mechanical microenvironment (TMME) severely restricts antitumor efficacy of prodrug nanomedicines by limiting drug delivery and fostering cancer stem cells (CSCs). Herein, we employed carbamate disulfide bridged doxorubicin dimeric prodrug as pharmaceutical ingredient, marketed IR780 iodide as photothermal agent, and biocompatible hydroxyethyl starch-folic acid conjugates as amphiphilic surfactant to prepare a theranostic nanomedicine (FDINs), which could actively target at TNBC 4T1 tumor tissues and achieve reduction-responsive drug release with high glutathione concentration in cancer cells and CSCs. Importantly, in addition to directly causing damage to cancer cells and sensitizing chemotherapy, FDINs-mediated photothermal effect regulates aberrant TMME via reducing cancer associated fibroblasts and depleting extracellular matrix proteins, thereby normalizing intratumor vessel structure and function to facilitate drug and oxygen delivery. Furthermore, FDINs potently eliminate CSCs by disrupting unique CSCs niche and consuming intracellular GSH in CSCs. As a result, FDINs significantly suppress tumor growth in both subcutaneous and orthotopic 4T1 tumors. This study provides novel insights on rational design of prodrug nanomedicines for superior therapeutic effect against stroma- and CSCs-rich solid malignancies.

A Two-Pronged Strategy for Enhanced Deep-Tumor Penetration and NIR-II Multimodal Imaging-Monitored Photothermal Therapy.

The second near-infrared (NIR-II)-induced photothermal therapy (PTT) has attracted a great deal of attention in recent years due to its non-invasiveness and because it uses less energy. However, the penetration of photothermal agents into solid tumors is seriously impeded by the dense-tumor extracellular matrix (ECM) containing cross-linked hyaluronic acid (HA), thereby compromising the ultimate therapeutic effects. Herein, acid-labile metal-organic frameworks were employed as nanocarriers to efficiently mineralize hyaluronidase (HAase) and encapsulate Ag2S nanodots by a one-pot approach under mild conditions. The obtained nanocomposites (AHZ NPs) maintained enzyme activity and changed in size to prolong blood circulation and complete delivery of the cargo to the tumor. Moreover, the released HAase could specifically break out the HA to loosen ECM and enable the Ag2S nanodots to breeze through the tumor matrix space and gain access to the deep tumor. Under near-infrared laser irradiation, the AHZ NPs displayed remarkable fluorescence, outstanding photoacoustic signals, and excellent photothermal properties in the whole tumor. This work offers a promising two-pronged strategy via a decrease in nanoparticle size and the degradation of dense ECM for NIR-II multimodal imaging-guided PTT of deep tumors.

Methylmercury-induced DNA methylation-From epidemiological observations to experimental evidence.

Methylmercury (MeHg) is a developmental neurotoxicant, and one potential mechanism of MeHg toxicity is epigenetic dysregulation. In a recent meta-analysis of epigenome-wide association studies (EWAS), associations between prenatal MeHg exposure and DNA methylation at several genomic sites were identified in blood from newborns and children. While EWASs reveal human-relevant associations, experimental studies are required to validate the relationship between exposure and DNA methylation changes, and to assess if such changes have implications for gene expression. Herein, we studied DNA methylation and gene expression of five of the top genes identified in the EWAS meta-analysis, MED31, MRPL19, GGH, GRK1, and LYSMD3, upon MeHg exposure in human SH-SY5Y cells exposed to 8 or 40 nM of MeHg during differentiation, using bisulfite-pyrosequencing and qPCR, respectively. The concentrations were selected to cover the range of MeHg concentrations in cord blood (2-8.5 µg/L) observed in the cohorts included in the EWAS. Exposure to MeHg increased DNA methylation at MED31, a transcriptional regulator essential for fetal development. The results were in concordance with the epidemiological findings where more MED31 methylation was associated with higher concentrations of MeHg. Additionally, we found a non-significant decrease in DNA methylation at GGH, which corresponds to the direction of change observed in the EWAS, and a significant correlation of GGH methylation with its expression. In conclusion, this study corroborates some of the EWAS findings and puts forward candidate genes involved in MeHg's effects on the developing brain, thus highlighting the value of experimental validation of epidemiological association studies.

Toxicity and Toxin Composition of the Greater Blue-Ringed Octopus Hapalochlaena lunulata from Ishigaki Island, Okinawa Prefecture, Japan.

The toxicity of the greater blue-ringed octopus Hapalochlaenalunulata, whose bite is fatal to humans, was examined to better understand and prevent deaths from accidental bites. Living specimens were collected from tide pools on Ishigaki Island, Okinawa Prefecture, Japan, in November and December of 2015, 2016, and 2017. The specimens were examined for the anatomical distribution of the toxicity, which was expressed in terms of mouse units (MU), by the standard bioassay method for tetrodotoxin (TTX) in Japan. Paralytic toxicity to mice was detected in all of the soft parts. The posterior salivary glands exhibited the highest toxicity score with a maximum level of 9276 MU/g, which was classified as "strongly toxic" (more than 1000 MU/g tissue) according to the classification of toxicity established by the Ministry of Health, Labor and Welfare of Japan, followed by the hepatopancreas (21.1 to 734.3 MU/g), gonads (not detectable to 167.6 MU/g), arms (5.3 to 130.2 MU/g), and other body areas (17.3 to 107.4 MU/g). Next, the toxin from the salivary glands was partially purified by a Sep-Pak C18 cartridge and an Amicon Ultra Centrifugal Filter with a 3000-Da cut-off, and analyzed by liquid chromatography-mass spectrometry (LC-MS) equipped with a φ2.0 × 150-mm (5 µm) TSKgel Amide-80 column (Tosoh, Tokyo, Japan) with a mixture of 16 mM ammonium formate buffer (pH 5.5) and acetonitrile (ratio 3:7, v/v) as a mobile phase. This study aimed to clarify the toxicity and the composition of TTX and its derivatives in this toxic octopus. The main toxin in this toxic octopus was identified as TTX, along with 4-epi TTX, 4, 9-anhydroTTX and 6-epi TTX. Further, the toxicity of this species is also significant from a food hygiene point of view.

GSTP1, ERCC1 and ERCC2 polymorphisms, expression and clinical outcome of oxaliplatin-based adjuvant chemotherapy in colorectal cancer in Chinese population.

AIM: Platinum agents have shown to be effective in the treatment of colorectal cancer. We assessed whether single nucleotide polymorphisms (SNPs) in GSTP1, ERCC1 Asn118Asn and ERCC2 Lys751Gln might predict the overall survival in patients receiving oxaliplatin-based chemotherapy in a Chinese population. METHODS: SNPs of GSTP1, ERCC1 Asn118Asn and ERCC2 Lys751Gln in 335 colorectal cancer patients were assessed using TaqMan nuclease assays. RESULTS: At the time of final analysis on Nov. 2011, the median follow-up period was 37.7 months (range from 1 to 60 months). A total of 229 patients died during follow-up. Our study showed GSTP1 Val/Val (HR=0.44, 95% CI=0.18-0.98), ERCC1 C/C (HR=0.20, 95% CI=0.10-0.79) and ERCC2 G/G (HR=0.48, 95% CI=0.19-0.97) to be significantly associated with better survival of colorectal cancer. GSTP1 Val/Val, ERCC1 C/C and ERCC2 G/G were also related to longer survival among patients with colon cancer, with HRs (95% CIs) of 0.41 (0.16-0.91), 0.16 (0.09-0.74) and 0.34 (0.16-0.91), respectively. CONCLUSION: GSTP1, GSTP1, ERCC1 Asn118Asn and ERCC2 Lys751Gln genotyping might facilitate tailored oxaliplatin-based chemotherapy for colorectal cancer patients.