Knockdown of the VEGFB/VEGFR1 signaling suppresses pubertal mammary gland development of mice via the inhibition of PI3K/Akt pathway.

Vascular endothelial growth factor B (VEGFB) has been well demonstrated to play a crucial role in regulating vascular function by binding to the VEGF receptors (VEGFRs). However, the specific role of VEGFB and VEGFRs in pubertal mammary gland development remains unclear. In this study, we observed that blocking the VEGF receptors with Axitinib suppressed the pubertal mammary gland development. Meanwhile, the proliferation of mammary epithelial cells (HC11) was repressed by blocking the VEGF receptors with Axitinib. Additionally, knockdown of VEGFR1 rather than VEGFR2 and NRP1 elicited the inhibition of HC11 proliferation, suggesting the essential role of VEGFR1 during this process. Furthermore, Axitinib or VEGFR1 knockdown led to the inhibition of the PI3K/Akt pathway. However, the inhibition of HC11 proliferation induced by Axitinib and or VEGFR1 knockdown was eliminated by the Akt activator SC79, indicating the involvement of the PI3K/Akt pathway. Finally, the knockdown of VEGFB and VEGFR1 suppressed the pubertal development of mice mammary gland with the inhibition of the PI3K/Akt pathway. In summary, the results showed that knockdown of the VEGFB/VEGFR1 signaling suppresses pubertal mammary gland development of mice via the inhibition of the PI3K/Akt pathway, which provides a new target for the regulation of pubertal mammary gland development.

Browning of Mammary Fat Suppresses Pubertal Mammary Gland Development of Mice via Elevation of Serum Phosphatidylcholine and Inhibition of PI3K/Akt Pathway.

Mammary fat plays a profound role in the postnatal development of mammary glands. However, the specific types (white, brown, or beige) of adipocytes in mammary fat and their potential regulatory effects on modulating mammary gland development remain poorly understood. This study aimed to investigate the role of the browning of mammary fat on pubertal mammary gland development and explore the underlying mechanisms. Thus, the mammary gland development and the serum lipid profile were evaluated in mice treated with CL316243, a ß3-adrenoceptor agonist, to induce mammary fat browning. In addition, the proliferation of HC11 cells co-cultured with brown adipocytes or treated with the altered serum lipid metabolite was determined. Our results showed that the browning of mammary fat by injection of CL316243 suppressed the pubertal development of mice mammary glands, accompanied by the significant elevation of serum dioleoylphosphocholine (DOPC). In addition, the proliferation of HC11 was repressed when co-cultured with brown adipocytes or treated with DOPC. Furthermore, DOPC suppressed the activation of the PI3K/Akt pathway, while the DOPC-inhibited HC11 proliferation was reversed by SC79, an Akt activator, suggesting the involvement of the PI3K/Akt pathway in the DOPC-inhibited proliferation of HC11. Together, the browning of mammary fat suppressed the development of the pubertal mammary gland, which was associated with the elevated serum DOPC and the inhibition of the PI3K/Akt pathway.

Protective effects of safranal on diabetic retinopathy in human microvascular endothelial cells and related pathways analyzed with transcriptome sequencing.

Aim: To determine the effect of safranal on diabetic retinopathy in vitro and its possible mechanisms. Methods: We used human retinal microvascular endothelial cells (HRMECs) to test the influence of safranal in vitro. High glucose damage was established and an safranal was tested at various concentrations for its potential to reduce cell viability using the MTT assay. We also employed apoptosis detection, cell cycle detection, a transwell test, and a tube formation assay to look into safranal's inhibitory effects on high glucose damage at various doses. Furthermore, mRNA transcriptome sequencing was performed. mRNA expression levels in a high glucose damage model, a high glucose damage model treated with safranal, and a blank control were compared to find the possible signaling pathway. Western blotting was used to confirm the expressions of several molecules and the levels of phosphorylation in each for the newly discovered pathway. Results: Cell proliferation was inhibited under a high glucose condition but could be protected by safranal at different concentrations (P<0.001). Flow cytometry results suggested safranal also protected cells from apoptosis (P=0.006). A transwell test demonstrated reduced invasiveness of safranal-treated cells in a high glucose condition (P<0.001). In a tube formation investigation, there were noticeably more new branches in the high gloucose group compared to a high glucose treated with safranal group (P<0.001). In mRNA expression patterns on transcriptome sequencing, the MAPK signaling pathway showed an expression ratio. With western blotting, the phosphorylation level of p38-AKT was elevated under a high glucose condition but could be inhibited by safranal. The expression of molecules associated with cell adhesion, including E-cadherin, N-cadherin, Snail, Twist, and fibronectin also changed significantly after safranal treatment under a high glucose condition. Conclusion: Safranal can protect diabetic retinopathy in vitro, and the p38-AKT signaling pathway was found to be involved in the pathogenesis of diabetic retinopathy and could be inhibited by safranal. This pathway may play a role by influencing cell migration and adhesion.

Effect of Graphene/Spherical Graphite Ratio on the Properties of PLA/TPU Composites.

Wave-absorbing materials are developing in the direction of "light weight, wide frequency band, thin layer and high strength", and it is difficult to achieve the synergy between wave-absorbing performance and mechanical properties when graphene absorbent is compounded with a single resin matrix. In this paper, based on the preparation of a new composite absorbing wire with a graphene (GR)/spherical graphite (SG) double absorbent and polylactic acid (PLA)/thermoplastic polyurethane (TPU) double matrix, we proposed a new method to prepare samples for testing the electromagnetic parameters and tensile strength by fused deposition modeling (FDM). Furthermore, the effect of SG/GR ratio on the microwave absorbing properties and mechanical properties of PLA/TPU composites was specifically studied. It was found that when the ratio of SG/GR was small (0:5, 1:4), the dielectric loss (interfacial polarization loss, dipole polarization loss, conductivity loss) and attenuation ability of the composites were stronger, and the impedance matching was better. When the SG/GR ratio was large (5:0, 4:1), the composites had high strength and toughness. When the ratio of SG/GR was moderate (2:3, 3:2), it could retain the absorbing and mechanical properties of the absorbing materials. On the one hand, the SG and PLA/TPU matrix formed an "island structure", which improves the dispersion of GR; on the other hand, the GR and PLA/TPU matrix formed a "core-shell structure", which promotes polarization and multiple scattering.

Psychological Distance Impacts Subgroup Reciprocity in Technological Innovation Networks: The Mediating Role of Divisive Faultlines.

As information flows at ever-increasing speeds across technological innovation networks, it is crucial to optimize reciprocity among partnering enterprises. However, the impact of psychological distance on subgroup reciprocity in such networks has not yet been investigated. To address this gap, the current study drew on theories of faultlines and cohesive subgroups to model the relationship between psychological distance and subgroup reciprocity within technological innovation networks. Our hypotheses were tested using data from 174 respondents working in Yunnan Province, China. The results were as follows: first, psychological distance had negative effects on subgroup reciprocity in technological innovation networks; second, relationship-divisive and innovation-divisive faultlines negatively impacted reciprocity within and between subgroups; third, the faultlines partially mediated the negative relationship between psychological distance and intra-subgroup reciprocity; and fourth, the negative relationship between psychological distance and subgroup reciprocity was not mediated by the faultlines. The findings uncover the psychological mechanism of subgroup reciprocity within technological innovation networks. They will inform the decision-making process of enterprises when selecting partners within their technological innovation networks and support the development of effective reciprocal relationships with other innovators.

Changes in the Foveal Outer Nuclear Layer of Central Serous Chorioretinopathy Patients Over the Disease Course and Their Response to Photodynamic Therapy.

OBJECTIVE: To investigate the association between foveal outer nuclear layer (ONL) thickness and the natural course of central serous chorioretinopathy (CSC), as well as the thickness change after photodynamic therapy (PDT), exploring the PDT timing for CSC. METHODS: This retrospective consecutive case series included 358 CSC patients between January 2014 and December 2019. All patients were divided into four groups depending on disease duration: Group A: ≤1 month; Group B: >1 and ≤3 months; Group C: >3 and≤6 months and Group D: >6 months. Foveal ONL thickness of the CSC eye and the clinically healthy fellow eye were measured and compared in all patients. Fifty-six patients were successfully treated with half-dose of PDT, showing complete subretinal fluid absorption, were followed up for more than 6 months and further investigated. The recovery of foveal ONL thickness was analyzed in the affected eyes of patients with different disease duration. RESULTS: No significant reduction was found in CSC foveal ONL thickness (µm) compared to the fellow eye in patients with disease duration less than 1 week (112.3 ± 12.2 vs. 116.7 ± 15.3, P = 0.268). Patients with longer disease duration had varying degrees of ONL thinning compared to the contralateral eye (all P < 0.05) and this difference was more pronounced in patients with disease duration greater than 6 months (75.8 ± 12.9 vs. 113.0 ± 11.5, P < 0.001). At 6-month follow-up after PDT, foveal ONL thickness of patients with <1 month disease duration recovered significantly from onset (97.3 ± 18.2 to 113.6 ± 8.7, P < 0.001) and became similar to that of the healthy fellow eye. Foveal ONL thickness of patients with duration>1 and≤3 months recovered significantly (88.5 ± 11.5 to 95.8 ± 11.3, P = 0.012) but remained thinner than that of the healthy fellow eye. Foveal ONL thickness did not improve significantly in cases with disease duration longer than 3 months (P > 0.05). CONCLUSION: Foveal ONL thinning was positively associated with disease duration prior to treatment suggesting that longer disease duration limits scope for foveal ONL recovery. CSC patients should be treated with PDT as soon as possible to prevent disease development and reduced visual function.

Mid-infrared supercontinuum generation in an all-fiberized Er-doped ZBLAN fiber amplifier.

A high power mid-infrared (MIR) supercontinuum (SC) is demonstrated in a strictly all-fiberized Er-doped ZBLAN fiber amplifier (EDZFA). The EDZFA is seeded by a 2.0-3.5 µm fiber-based SC laser and pumped at 976 nm. At pulse repetition rate of 500 kHz, the output SC spanning from 2.7 to 4.2 µm reaches a record output power of 4.96 W with an overall slope efficiency of 17.3%. This Letter, to the best of our knowledge, demonstrates the first all-fiberized in-amplifier SC generation in the MIR region, which has significant potential for further power scaling.

High-power mid-infrared supercontinuum generation in a fluoroindate fiber with over 2 W power beyond 3.8 µm.

An all-fiber mid-infrared supercontinuum (MIR-SC) laser source with a power of over 2 W beyond 3.8 µm is demonstrated. The SC laser involves a silica-fiber-based SC laser as a pump source and a piece of fluoroindate (InF3) fiber as a nonlinear medium. The influence of pump pulse repetition rate on the SC characteristics is carefully studied. In the InF3 fiber, the pump pulse with spectral coverage of 1.9-2.6 µm is converted into MIR-SC with a broadest spectral coverage of 1.9-4.9 µm and a maximal average power of 11.8 W. Up to 2.18 W is measured in the spectral region beyond 3.8 µm, which, to the best of the authors' knowledge, demonstrates the record SC power in this waveband to date.

Privacy-Preserving Data Aggregation against False Data Injection Attacks in Fog Computing.

As an extension of cloud computing, fog computing has received more attention in recent years. It can solve problems such as high latency, lack of support for mobility and location awareness in cloud computing. In the Internet of Things (IoT), a series of IoT devices can be connected to the fog nodes that assist a cloud service center to store and process a part of data in advance. Not only can it reduce the pressure of processing data, but also improve the real-time and service quality. However, data processing at fog nodes suffers from many challenging issues, such as false data injection attacks, data modification attacks, and IoT devices' privacy violation. In this paper, based on the Paillier homomorphic encryption scheme, we use blinding factors to design a privacy-preserving data aggregation scheme in fog computing. No matter whether the fog node and the cloud control center are honest or not, the proposed scheme ensures that the injection data is from legal IoT devices and is not modified and leaked. The proposed scheme also has fault tolerance, which means that the collection of data from other devices will not be affected even if certain fog devices fail to work. In addition, security analysis and performance evaluation indicate the proposed scheme is secure and efficient.