Gestational and Lactational Co-Exposure to DEHP and BPA Impairs Hepatic Function via PI3K/AKT/FOXO1 Pathway in Offspring.

Di-(2-Ethylhexyl) phthalate (DEHP) and bisphenol A (BPA) present significant environmental endocrine-disrupting chemical properties. Although studies have implied reproductive impairment from exposure to BPA and DEHP, no study to date has shown the effect and mechanism of hepatic function after gestational and lactational co-exposure to DEHP and BPA in offspring. A total of 36 perinatal rats were randomly divided into four groups, DEHP (600 mg/kg/day), BPA (80 mg/kg/day), DEHP combined with BPA (600 mg/kg/day + 80 mg/kg/day), and control. Notably, 11 chemical targets were screened after identifying eight substances associated with chemically-induced hepatic damage. Molecular docking simulations revealed a high-scoring combination of eight metabolic components and targets of the PI3K/AKT/FOXO1 signaling pathway. The DEHP and BPA combination disrupted hepatic steatosis, ultimately affecting systemic the glucose and the lipid metabolic homeostasis with significant toxicity. Mechanistically, co-exposure to DEHP and BPA causes liver dysfunction and hepatic insulin resistance via PI3K/AKT/FOXO1 pathway in offspring. This is the first study of the hepatic function and mechanism of co-exposure to DEHP and BPA that combines metabolomics, molecular docking, and traditional toxicity assessment methods.

Optical trapping and manipulation of massive particles based on spatial diffraction of a 45° tilted fiber Bragg grating.

In this work, we proposed an optical trapping and manipulation technology based on spatial diffraction of 45° tilted fiber Bragg grating (TFBG). The length of the line-shape-facula of the TFBG diffraction light can be as large as tens of millimeters, which enables the TFBG trapping system control massive dielectric particles. We analyze the light distribution of the spatial diffraction by using the volume current method (VCM) and established a theoretical model to analyze the optical trapping force of TFBG based on the ray tracing method (RTM). Then, we designed several optical trapping schemes, with two-, three- and four-TFBGs respectively. Numeral simulation indicates that only the scheme with axisymmetric layout of TFBGs can achieve stable particle trapping. We comprehensively analyze the trapping force distribution of four- TFBG scheme with different influence factors. In addition, the rotation manipulation based on the two- and four- TFBGs schemes are also demonstrated. The proposed optical trapping technology open a new route for massive particles trapping and manipulation.

Proteomics unite traditional toxicological assessment methods to evaluate the toxicity of iron oxide nanoparticles.

Iron oxide nanoparticles (IONPs) are the first generation of nanomaterials approved by the Food and Drug Administration for use as imaging agents and for the treatment of iron deficiency in chronic kidney disease. However, several IONPs-based imaging agents have been withdrawn because of toxic effects and the poor understanding of the underlying mechanisms. This study aimed to evaluate IONPs toxicity and to elucidate the underlying mechanism after intravenous administration in rats. Seven-week-old rats were intravenously administered IONPs at doses of 0, 10, 30, and 90 mg/kg body weight for 14 consecutive days. Toxicity and molecular perturbations were evaluated using traditional toxicological assessment methods and proteomics approaches, respectively. The administration of 90 mg/kg IONPs induced mild toxic effects, including abnormal clinical signs, lower body weight gain, changes in serum biochemical and hematological parameters, and increased organ coefficients in the spleen, liver, heart, and kidneys. Toxicokinetics, tissue distribution, histopathological, and transmission electron microscopy analyses revealed that the spleen was the primary organ for IONPs elimination from the systemic circulation and that the macrophage lysosomes were the main organelles of IONPs accumulation after intravenous administration. We identified 197 upregulated and 75 downregulated proteins in the spleen following IONPs administration by proteomics. Mechanically, the AKT/mTOR/TFEB signaling pathway facilitated autophagy and lysosomal activation in splenic macrophages. This is the first study to elucidate the mechanism of IONPs toxicity by combining proteomics with traditional methods for toxicity assessment.

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.

Wideband frequency-tunable optoelectronic oscillator with a directly modulated AlGaInAs/InP integrated twin-square microlaser.

We propose and demonstrate an optoelectronic oscillator with a directly modulated AlGaInAs/InP integrated twin-square microlaser for generating wideband frequency-tunable microwave signals with low phase noise. Apart from the relaxation oscillation peak, the modulation response of the twin-square microlaser working at the mutual optical injection state exhibits a significant enhancement around the beating frequency of the lasing modes in the two square cavities owing to the photon-photon resonance. A self-sustaining oscillation can be generated around the modulation response peak with the lowest loop loss occurring at the relaxation oscillation frequency or the beating frequency, depending on the practical state of the twin-square microlaser. High-quality tunable microwave signals ranging from 2.22 to 19.52 GHz are generated with single sideband phase noises below -110 dBc/Hz at the 10 kHz offset frequency and side-mode suppression ratios of approximately 40 dB by tuning the injection currents of the twin-square microlaser.

Narrow-linewidth microwave generation by an optoelectronic oscillator with a directly modulated microsquare laser.

A simple dual-loop optoelectronic oscillator using a 16 µm side length AlGaInAs/InP directly modulated microsquare laser is proposed and investigated without an external modulator. High-performance first harmonics are realized, with 3 dB linewidth, less than 200 Hz, and a frequency-tunable range from 2 to 8 GHz. Meanwhile, a side-mode suppression ratio of 60 dB is obtained for the microwave by the dual-loop structure. Within the whole tuning range, the measured single-sideband phase noises of the first harmonics are about -110 dBc/Hz at 10 kHz frequency offset. Furthermore, the second and third harmonics with frequency-tunable ranges from 4 to 16 GHz and 6 to 24 GHz are achieved as well.

Porcine circovirus type 2 increases interleukin-1beta and interleukin-10 production via the MyD88-NF-kappa B signaling pathway in porcine alveolar macrophages in vitro.

Porcine alveolar macrophages (PAMs) represent the first line of defense in the porcine lung after infection with porcine circovirus type 2 (PCV2) via the respiratory tract. However, PCV2 infection impairs the microbicidal capability of PAMs and alters cytokine production and/or secretion. At present, the reason for the imbalance of cytokines has not been fully elucidated, and the regulatory mechanisms involved are unclear. In this study, we investigated the expression levels and regulation of interleukin-1beta (IL-1ß) and IL-10 in PAMs following incubation with PCV2 in vitro. Levels of IL-1ß and IL-10 increased in PAM supernatants, and the distribution of nuclear factor kappa B (NF-κB) p65staining in nucleus, expression of MyD88 and p-IκB in cytoplasm, and DNA-binding activity of NF-κB increased after incubation with PCV2, while p65 expression in PAM cytoplasm decreased. However, when PAMs were co-incubated with PCV2 and small interfering RNA targeting MyD88, those effects were reversed. Additionally, mRNA expression levels of Toll-like receptors (TLR)-2, -3, -4, -7, -8, and -9 increased when PAMs were incubated with PCV2. These results show that PCV2 induces increased IL-1ß and IL-10 production in PAMs, and these changes in expression are related to the TLR-MyD88-NF-κB signaling pathway.

Porcine circovirus type 2 induces type I interferon production via MyD88-IKKα-IRFs signaling rather than NF-κB in porcine alveolar macrophages in vitro.

Type I interferon (IFN-I) plays important roles in host antiviral responses. The interferon regulatory factor (IRF) and NF-κB transcription factors are thought to be important in the processes of viral secretion and triggering of interferon production. Recently, studies have shown that porcine circovirus type 2 (PCV2) can induce IFN-I production in vivo and in vitro, but the mechanisms underlying the production of PAMs infected with PCV2 remains unknown. Treatment of these cells with BAY11-7082, an inhibitor of NF-κB activation, allowed us to study the secretion of IFN-α and IFN-ß in PAMs infected with PCV2. We found that IFN-α expression was induced following virus infection of PAMs. Notably, even after inhibitor treatment of PAMs infected with PCV2, secretion of IFN-α was significantly higher (P<0.05) compared with the PCV2 infection alone group. Our findings suggest that NF-κB plays a minor role in PCV2-induced type I interferon responses. To further characterize the signaling pathway that drives IFN-I expression in PAMs in response to PCV2, we used siRNA to silence the expression of Myeloid differentiation factor 88 (MyD88) and study the role of MyD88-IKKα-IRF signaling in IFN-I production in PAMs induced by PCV2. Our findings show that PCV2 induced IFN-α mRNA transcription, which is associated with the activities of MyD88, IRF7, and IRF3. Thus, PCV2 can induce IFN-I transcription via the MyD88-IKKα-IRF signaling axis.

Activation of the TLR/MyD88/NF-κB signal pathway contributes to changes in IL-4 and IL-12 production in piglet lymphocytes infected with porcine circovirus type 2 in vitro.

Porcine circovirus type 2 (PCV2) causes immunosuppression in pigs. One causative factor is an imbalance in cytokine levels in the blood and lymphoid tissues. Many studies have reported changes in cytokine production, but the regulatory mechanisms involved have not yet been elucidated. In this study, we investigated alteration and regulation of IL-4 and IL-12 production in lymphocytes following incubation with PCV2 in vitro. The levels of IL-4 decreased and levels of IL-12 increased in lymphocyte supernatants, and the DNA-binding activity of NF-κB and the expression of p65 in the nucleus and p-IκB in the cytoplasm of lymphocytes increased after incubation with PCV2. However, these effects were reversed when lymphocytes were coincubated with PCV2 and the NF-κB inhibitor BAY11-7082. In addition, the expression of MyD88 protein increased and the expression of mRNA for the toll-like receptors (TLRs) TLR2, TLR3, TLR4 and TLR9 was upregulated when lymphocytes were incubated with PCV2. However, no change was seen in TLR7 and TLR8 mRNA expression. In conclusion, this study showed that PCV2 induced a decrease in IL-4 and an increase in IL-12 production in lymphocytes, and these changes were regulated by the TLR-MyD88-NF-κB signal pathway.